Formic Acid → (R)-6,6-Difluoro-5-(2-fluoro-5-pyrimidin-5-yl-phenyl)-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine formate

Participants

Reaction Conditions

Reaction Steps

A degassed solution of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5-methyl-2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (20 mg, 59.3 μmol (intermediate A7.1), pyrimidine-5-boronic acid (8.8 mg, 71.2 μmol), and cesium carbonate (77.3 mg, 237 μmol) in a mixture of dimethoxyethane (1 ml) and water (0.5 ml) was treated in a tube under an argon atmosphere with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (CAS 72287-26-4) (2.2 mg, 3.0 μmol). The tube was sealed and heated to 80° C. for 70 minutes. In order to complete the reaction, pyrimidine-5-boronic acid (2.2 mg, 17.8 μmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (2.2 mg, 3.0 μmol) were added and stirring continued at 80° C. for 10 minutes. For the workup, the reaction mixture was cooled to room temperature and diluted with water (1.5 ml). After addition of formic acid (0.5 ml) the mixture was filtrated and the filtrate purified by preparative HPLC. The (R)-6,6-difluoro-5-(2-fluoro-5-pyrimidin-5-yl-phenyl)-5-methyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine was obtained as a light brown amorphous material (n off-white solid (14 mg, 59% yield). MS (ISP): m/z=337.2 [M+H]+.

Provenance & Evidence