Diisopropylethylamine → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3-fluoroazetidin-1-yl)pyrimidin-5-yl]-4-tert-butyl-1,3-thiazol-2-yl}-3-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

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, 180 mg, 0.106 mmol) in THF (5 mL) was added 3-fluoroazetidine hydrochloride (35.4 mg, 0.317 mmol) and DIEA (0.092 mL, 0.529 mmol). It 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 (74 mg, 93% yield). LCMS (M+H)+: 752.05. 1H NMR (CDCl3, 500 MHz): δ8.36 (s, 1H), 8.08 (s, 1H), 8.00 (s, 1H), 7.93 (s, 1H), 7.87 (m, 1H), 7.79 (s, 2H), 5.80 (d, 9.0 Hz, 1H), 4.75 (m, 4H), 4.61-4.53 (m, 4H), 4.47 (m, 1H), 4.09 (m, 1H), 3.76 (s, 3H), 1.33 (s, 9H), 0.82 (d, 7.0 Hz, 3H). RTA IC50: 197 nM.

Provenance & Evidence