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-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid (INTERMEDIATE 52, 80 mg, 0.106 mmol) in THF (5 mL) was added 3,3-difluoroazetidine hydrochloride (41.1 mg, 0.317 mmol) and DIEA (0.092 mL, 0.529 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 water and acetonitrile (10% to 100%), to give the title compound as a yellowish solid after lyophilization (72 mg, 88% yield). LCMS (M+H)+: 770.1. 1H NMR (CDCl3, 500 MHz): δ 8.35 (s, 1H), 8.08 (s, 1H), 8.00 (s, 1H), 7.93 (s, 1H), 7.87 (m, 1H), 7.79 (s, 2H), 5.82 (d, 9.0 Hz, 1H), 5.50 (m, 1H), 4.75 (m, 1H), 4.58-4.34 (m, 4H), 4.09 (m, 1H), 3.75 (s, 3H), 1.33 (s, 9H), 0.81 (d, 7.0 Hz, 3H). RTA IC50: 800 nM.

1. customThe solvent was evaporated
2. customthe residue was purified on reverse phase HPLC
3. washeluting with water and acetonitrile (10% to 100%)