反应详情

温度

90 °C

To a solution of methyl 1-(2-(5-(5-bromopyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate 47 (0.24 mmol) in 1,4-dioxane (2.0 mL) is added 2-(4-(difluoromethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 7 (0.28 mmol), 1.8M K2CO3 (0.5 mmol) and Pd(PPh3)4 (0.017 mmol). The reaction is evacuated and backfilled with nitrogen twice then heated at 90° C. for 12 h. The reaction mixture is cooled to rt, diluted with water (10 mL) and extracted with DCM (2×20 mL). The organic layer is separated, dried over Na2SO4 and concentrated. Purification by preparative HPLC (ACN gradient 20-70%) affords methyl 1-(2-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-fluorophenoxy)ethyl)piperidine-4-carboxylate 48 as white solid. MS (m/z) (M+1)+: 517.1.

1. customThe reaction is evacuated
2. temperatureThe reaction mixture is cooled to rt
3. additiondiluted with water (10 mL)
4. extractionextracted with DCM (2×20 mL)
5. customThe organic layer is separated
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customPurification by preparative HPLC (ACN gradient 20-70%)