反应详情

温度

65 °C

A mixture of 2-(3-bromoimidazo[1,2-α]pyrimidin-7-yl)propan-2-ol (256 mg, 1.0 mmol) and 2,4-difluoro-3-(pyridin-3-yl)benzeneboronic acid (352 mg, 1.5 mmol) in tetrahydrofuran (3 ml) and sodium carbonate (1.25 ml of a 2M solution in water, 2.5 mmol) was degassed with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added and this mixture was heated at 65° C. for 24 h. The reaction was cooled to ambient temperature then partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate. The organics were dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica gel eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%) gave 2-[3-(2,4-difluoro-3-(pyridin-3-yl)phenyl)imidazo[1,2-α]pyrimidin-7-yl]propan-2-ol as a pale yellow oil which solidified on standing (200 mg, 44%). Bis-hydrochloride salt (from ethyl acetate/ethanol): δH (360 MHz, d6-DMSO) 1.56 (6H, s), 7.62 (1H, t, J 9), 7.79-7.84 (1H, m), 7.86 (1H, s), 7.88 (1H, s), 8.32 (1H, d, J 8), 8.54 (1H, s), 8.80 (1H, d, J 5), 8.98 (1H, s), 9.27 (1H, dd, J 7 and 3).

1. customwas degassed with nitrogen for 10 min
2. temperatureThe reaction was cooled to ambient temperature
3. customthen partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate
4. dry with materialThe organics were dried over anhydrous magnesium sulfate
5. filtrationfiltered and pre-adsorbed onto silica
6. customPurification by chromatography on silica gel eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%)