反应详情

温度

80 °C

In a tube a mixture of [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-4-[5-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-2,4-difluoro-phenyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amine (intermediate D1.1) (130 mg, 144 μmol), 2,6-dichlorobenzo[d]oxazole (30.4 mg, 159 μmol), and cesium carbonate (188 mg, 576 μmol) in tetrahydrofuran (4 ml) and water (2 ml) was purged with argon for 5 minutes. Thereafter, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (5.88 mg, 7.21 μmol) was added, the tube was sealed and the mixture heated at 80° C. for 16 hours. After evaporation, the residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 70:30 as the eluent. The [bis-(4-methoxy-phenyl)-phenyl-methyl]-{(R)-4-[5-(6-chloro-benzooxazol-2-yl)-2,4-difluoro-phenyl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-yl}-amine (52 mg, 50% yield) was obtained as a pale yellow solid. MS (ISP): m/z=716.1 [M+H]+.

1. customwas purged with argon for 5 minutes
2. customthe tube was sealed
3. customAfter evaporation
4. customthe residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 70:30 as the eluent