Potassium Carbonate → (R)-5-(1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amine

HRID 1485449Notes

Reaction equation

HRID 1485449 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH3:15])=[N:13][N:14]=[C:10]3[C@H:9]([CH3:16])[CH2:8][N:7]([C:17]3[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=3)[C:6]=2[CH:23]=1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[CH:34][C:35]([NH2:38])=[N:36][CH:37]=2)O1.[F-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C.C1(C)C=CC=CC=1>[CH3:15][C:12]1[N:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:32]4[CH:33]=[CH:34][C:35]([NH2:38])=[N:36][CH:37]=4)=[CH:23][C:6]=3[N:7]([C:17]3[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=3)[CH2:8][C@@H:9]([CH3:16])[C:10]2=[N:14][N:13]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 522689Potassium FluorideHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 70979194(R)-8-bromo-1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine

Product 1

HCID 70978957(R)-5-(1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amineYield 26%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of (R)-8-bromo-1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepine (38 mg, 0.1 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (44 mg, 0.2 mmol), tetrakis(triphenylphosphine)palladium(0) (12 mg, 0.02 mmol), potassium fluoride (5.8 mg, 0.1 mmol) and potassium carbonate (49 mg, 0.15 mmol) in a mixed solution of toluene (2 mL), ethanol (1 mL) and water (0.2 mL) was heated at 115° C. for 1.5 hours under microwave (pressure: 2.0 bar, equipment power: 150 W). The reaction mixture was diluted with ethyl acetate (20 mL) and washed with brine (10 mL×3). The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to give a residue which was purified by column chromatography (silica gel, dichloromethane/methanol=8:1) to afford (R)-5-(1,4-dimethyl-6-(1-methyl-1H-pyrazol-4-yl)-5,6-dihydro-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-8-yl)pyridin-2-amine as a white solid (10 mg, 26%).

Workup

  1. washwashed with brine (10 mL×3)
  2. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. customto give a residue which
  6. customwas purified by column chromatography (silica gel, dichloromethane/methanol=8:1)

Sources & evidence

ORD record
ord-d1ae9232fd064a8bae942fbcb3da0baf
Source dataset
uspto-grants-2016_08
Patent number
US09422292B2

Reaction notes

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