Morpholine → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(morpholin-4-yl)pyrimidin-5-yl]-4-methyl-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-methyl-1,3-thiazol-2-yl}-3-methylbenzoic acid (INTERMEDIATE 54, 200 mg, 0.280 mmol) in THF (5 mL) was added morpholine (73.1 mg, 0.840 mmol) and DIEA (0.244 mL, 1.399 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 10%-100% acetonitrile in water to give the title compound as a white solid. LCMS (M+H)+: 728.1. 1H NMR (CDCl3, 500 MHz): δ 8.33 (s, 1H), 8.08 (s, 1H), 8.02 (d, J=8.5 Hz, 1H), 7.92 (s, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.77 (s, 2H), 5.75 (d, J=8.5 Hz, 1H), 4.77 (d, J=17.0 Hz, 1H), 4.36 (m, 1H), 4.086 (d, J=17.0 Hz, 1H), 3.92 (m, 4H), 3.85 (m, 4H), 2.71 (s, 3H), 2.44 (s, 3H), 0.78 (d, J=7.0 Hz, 3H). RTA IC50: 82 nM.

Provenance & Evidence