Citric Acid → HCID 72192441, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.218 mL, 1.566 mmol) was added to a mixture of THF (2 mL), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-{2-methoxy-5-[(2RS)-1,1,1-trifluoro-2-hydroxypropan-2-yl]pyridin-3-yl}-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (Step B, 220 mg, 0.313 mmol) and 3-fluoroazetidine hydrochloride (105 mg, 0.939 mmol). The reaction was placed under nitrogen and heated to 60° C. for 45 minutes; LCMS showed complete conversion to product. The reaction was diluted with 20 mL ethyl acetate and poured into 20 mL 10% citric acid, The organic layer was washed with 30 mL brine, then dried over sodium sulfate and concentrated. Purification on an X-Bridge 21.2×150 mm RP column with sample loaded using 7:3:1 CH3CN/water/DMSO (3 mL) employed a 10-100% acetonitrile/water (0.1% NH4OH) linear gradient at 15 mL/minutes over 20 minutes. The product of interest eluted in 70% portion of the above gradient. Rich cut of pure product peak was lyophilized to give product as a white solid. LCMS (M+H)+: 698.5. 1H NMR (500 MHz, CDCl3): 1:1 diasteromeric mixture: δ 8.38 (m, 1H), 8.26 (s, 0.5H), 8.24 (s, 0.5H), 7.91 (bs, 1H), 7.82 (m, 0.5H), 7.79 (d, J=2.2 Hz, 0.5H), 7.74 (s, 1H), 7.71 (s, 1H), 5.62 (d, J=8.4 Hz, 0.5H), 5.55 (m, 0.5H), 5.44 (m, 0.5H), 4.86 (m, 0.5H), 4.72 (d, J=16.5 Hz, 0.5H), 4.52 (m, 2.5H), 4.33 (m, 3H), 4.00 (s, 1.5H), 3.42 (bs, 0.5H), 3.28 (s, 0.5H), 3.99 (s, 1.5H), 1.85 (s, 3H), 0.77 (d, J=6.6 Hz, 1.5H), 0.73 (d, J=6.6 Hz, 1.5H). RTA IC50: 14 Nm.

Provenance & Evidence