反应详情

温度

60 °C

Using the procedures described in example 17 (trans)-4-(benzyloxycarbonylamino)cyclohexanecarboxylic acid was used to prepare (trans)-4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)cyclohexanamine. The latter compound (0.217 mmol, 67.1 mg) was dissolved in N,N-dimethylformamide, potassium carbonate (0.651 mmol, 90 mg) was added followed by 2-bromo-1,1-difluoroethane (0.217 mmol, 17.47 μl, 31.5 mg) and the reaction mixture was stirred in the micro wave at 60° C. After one hour another amount of 2-bromo-1,1-difluoroethane (0.217 mmol, 17.47 μl, 31.5 mg) was added and the reaction mixture was stirred in the micro wave at 60° C. for another hour. The reaction mixture was filtered, the filter was rinsed with acetonitrile and the filtrate was concentrated. The residue was purified by column chromatography (silica gel, gradient dichloromethane/methanol 10/0 to 9/1) to give (trans)-4-(1-bromo-8-methylimidazo[1,5-a]pyrazin-3-yl)-N-(2,2-difluoroethyl)cyclohexanamine (39.8 mg).

1. stirringthe reaction mixture was stirred in the micro wave at 60° C. for another hour
2. filtrationThe reaction mixture was filtered
3. washthe filter was rinsed with acetonitrile
4. concentrationthe filtrate was concentrated
5. customThe residue was purified by column chromatography (silica gel, gradient dichloromethane/methanol 10/0 to 9/1)