反应详情

温度

100 °C

Tris(dibenzylideneacetone)dipalladium(0) (1.786 g, 1.95 mmol) and 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (1.354 g, 2.34 mmol) were dissolved in toluene (40 mL) in a 100 mL two-necked round-bottomed flask equipped with a condensor and activated at 50 °C for 30 min under argon. In a 2 L reactor 5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine (36.0 g, 130 mmol), 4-(4-bromobenzyl)morpholine (34.8 g, 136 mmol), Sodium tert-pentoxide (22.91 g, 208.00 mmol) were dissolved in degassed toluene (960 mL) by heating at 100 °C. The preactivated catalyst solution was added to the mixture. It was put under nitrogen atmosphere carefully and stirred at 100 °C. The reaction was monitored by HPLC. After 20 h 38 % conversion was obtained. An extra batch of preactivated catalyst (3 %) in toluene (40 mL) was added and the mixture was stirred at 100 °C under nitrogen. After 52 h 92 % conversion was detected. Then the reaction mixture was cooled to room temperature, diluted with DCM (8 L) and extracted with water (3*5L). The separated organic phase was washed with brine and dried over Na2SO4. Filtration and concentration afforded orange solid which was slurried in EtOAc (100 mL) and stirred at reflux point for 30 min. Then it was cooled to room temperature and filtered. Yellow filtercake was obtained which was washed with EtOAc (150 ml). It was reslurried in EtOAc (100 mL) and stirred at reflux point for 30 min. Then it was cooled to room temperature and filtered. The filtercake was washed with EtOAc (150 ml) and dried in vacuo. Light yellow fine powder was obtained.