2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone → (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Participants

Reaction Steps

A dispersion of 2-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenoxy]-1-(5-chloro-pyridin-2-yl)-ethanone (160 mg, 349 μmol) and Raney Nickel (30 mg) in methanol (22 ml) was hydrogenated. For the workup, the reaction mixture was filtered through glass fiber paper and the solution was evaporated at reduced pressure. The crude product was purified by flash chromatography on a silica-NH2 phase using a gradient of heptane/ethyl acetate=100:0 to 0 to 100 as the eluent. The (R)-4-[(RS)-3-(5-chloro-pyridin-2-yl)-7-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine was obtained as a red solid. MS (ISP): m/z=413.2 [M+H]+.

Provenance & Evidence