Dichloromethane → (R)-5,5-Difluoro-4-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Participants

Reaction Conditions

Reaction Steps

In a tube a mixture of (R)-4-(5-bromo-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A6.1) (60 mg, 186 μmol), 1-(4-fluorophenyl)-1H-pyrazol-4-ylboronic acid (39.0 mg, 186 μmol), and cesium carbonate (242 mg, 743 μmol) in tetrahydrofuran (4 ml) and water (2 ml) was purged with argon for minutes. Thereafter, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (7.58 mg, 9.28 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 a silica-NH2 phase using a gradient of heptane/ethyl acetate=100:0 to 40:60 as the eluent. The (R)-5,5-Difluoro-4-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (36 mg, 48% yield) was obtained as a yellow solid. MS (ISP): m/z=405.0 [M+H]+.

Provenance & Evidence