反应详情

温度

60 °C

To a solution of 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfonyl)pyrimidin-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid (INTERMEDIATE 54, 200 mg, 0.280 mmol) in THF (5 mL) was added 3,3-difluoroazetidine (129.5 mg, 0.840 mmol) and DIEA (0.244 mL, 1.399 mmol). The reaction mixture was stirred at 60° C. for 15 minutes to see complete conversion by LCMS. The solvent was evaporated, and the residue was purified on reverse phase HPLC, eluting with 10%-100% acetonitrile in water, to give title compound as a slightly yellow solid. LCMS (M+H)+: 728.1. 1H NMR (CDCl3, 500 MHz): δ 8.37 (s, 1H), 8.08 (s, 1H), 8.02 (d, J=8.5 Hz, 1H), 7.93 (s, 1H), 7.90 (d, J=8.5 Hz, 1H), 7.78 (s, 2H), 5.79 (d, J=8.5 Hz, 1H), 4.78 (d, J=17.0 Hz, 1H), 4.58 (m, 4H), 4.42 (m, 3H), 4.08 (d, J=17.0 Hz, 1H), 2.72 (s, 3H), 2.43 (s, 3H), 0.80 (d, J=7.0 Hz, 3H). RTA IC50: 61 nM.

1. customThe solvent was evaporated
2. customthe residue was purified on reverse phase HPLC
3. washeluting with 10%-100% acetonitrile in water