反应详情

温度

115 °C

A mixture of (R)-tert-butyl 1-(6-chloro-5-cyanopyrazin-2-yl)piperidin-3-ylcarbamate (400 mg, 1.19 mmol), (4-aminophenyl)(morpholino)methanone (490 mg, 2.38 mmol), Pd(OAc)2 (54 mg, 0.24 mmol), BINAP (150 mg, 0.24 mmol), fine powder Cs2CO3 (1.55 g, 4.76 mmol) in dioxane (40 mL) was degassed with nitrogen stream for 3 min. The mixture was stirred in a nitrogen atmosphere at 115° C. for 2.5 h. The mixture was cooled, diluted with 100 mL EtOAc, filtered through celite, and concentrated in vacuo. The residue was subjected to flash column chromatography with 0 to 65% EtOAc in DCM to give (R)-tert-butyl 1-(5-cyano-6-(4-(morpholine-4-carbonyl)phenylamino)pyrazin-2-yl)piperidin-3-ylcarbamate (88) (yield >85%).

1. customwas degassed with nitrogen stream for 3 min
2. temperatureThe mixture was cooled
3. additiondiluted with 100 mL EtOAc
4. filtrationfiltered through celite
5. concentrationconcentrated in vacuo