反应详情

温度

85 °C

A dried pressure tube was consecutively charged with (R)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (intermediate B9.1) (199 mg, 299 μmol), 1,2-dimethoxyethane (4 ml), 1-(3-chlorophenyl)-1H-pyrazol-4-ylboronic acid (CAS 1072945-88-0) (102 mg, 448 μmol), and a solution of potassium carbonate (2M, 448·1). The tube was flushed with argon, thereafter tetrakistriphenylphosphinepalladium(0) (17.3 mg, 14.9 μmol) was added, the tube was sealed and the reaction mixture heated at 85° C. for 16 hours. For the workup, the reaction mixture was evaporated at reduced pressure and the residue directly purified by chromatography on an amine-silica phase using a gradient of heptane/ethyl acetate=100:0 to 80:20 as the eluent. The [bis-(4-methoxy-phenyl)-phenyl-methyl]-((R)-5-{5-[1-(3-chloro-phenyl)-1H-pyrazol-4-yl]-2-fluoro-phenyl}-6,6-difluoro-5,7,7-trimethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl)-amine (177 mg, 77% yield) was obtained as a white foam. MS (ISP): m/z=765.4 [M+H]+ and 767.4 [M+2+H]+.

1. customThe tube was flushed with argon
2. customthe tube was sealed
3. customFor the workup, the reaction mixture was evaporated at reduced pressure
4. customthe residue directly purified by chromatography on an amine-silica phase