反应详情

温度

80 °C

A mixture of 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (167 mg, 0.471 mmol), 3-amino-4-chloro-5-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)benzonitrile (150 mg, 0.471 mmol), palladium(II) acetate (28.0 mg, 0.125 mmol), XANTPHOS (27.2 mg, 0.047 mmol), DPPF (26.1 mg, 0.047 mmol) and cesium carbonate (399 mg, 1.223 mmol) in dioxane (5 ml) was evacuated and back filled with nitrogen three time and was heated at 80° C. for 3 h. The reaction mixture was filtered through a celite pad and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 10% to 100% EtOAc in Hexane) to give (+/−)-2-((2-chloro-5-cyano-3-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (137 mg) as a light yellow solid.

1. customwas evacuated
2. additionback filled with nitrogen three time
3. filtrationThe reaction mixture was filtered through a celite pad
4. concentrationthe filtrate was concentrated
5. customThe crude product was purified by flash chromatography on silica gel using
6. washan automated ISCO system (24 g column, eluting with 10% to 100% EtOAc in Hexane)