Hydrochloric Acid → HCID 72191836, compound

Participants

Reaction Conditions

Reaction Steps

(4S,5R)-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-5-(3,5-difluorophenyl)-4-methyl-1,3-oxazolidin-2-one (Step A, 519 mg, 0.989 mmol) and 3-fluoroazetidine hydrochloride (331 mg, 2.97 mmol) were placed in a microwave vial and suspended in THF (3 mL). Et3N (0.689 mL, 4.94 mmol) was added, the vial was sealed and the reaction heated to 100° C. for 20 minutes in a microwave reactor. LCMS showed complete conversion to product. The reaction was diluted with ethyl acetate (50 mL) and poured into 0.1N HCl solution (50 mL). The ethyl acetate layer was washed with brine (50 mL), dried over sodium sulfate and concentrated on rotary evaporator. Silica gel purification employing a 0-50% ethyl acetate/hexanes linear gradient followed by isocratic elution at 50% ethyl acetate/hexanes gave the product as a pale yellow solid. LCMS (M+H)+: 520.3. 1H NMR (500 MHz, CDCl3): δ 8.19 (d, J=2.5 Hz, 1H), 8.14 (s, 1H), 7.48 (d, J=2.5 Hz, 1H), 6.84 (m, 3H), 5.52 (m, 1.5H), 5.42 (m, 0.5H), 4.64 (d, J=17.3 Hz, 1H), 4.49 (m, 2H), 4.35 (m, 2H), 3.98 (d, J=17.3 Hz, 1H), 4.07 (m, 4H), 3.95 (s, 3H), 0.78 (d, J=6.6 Hz, 3H). SPA IC50: 728 nM.

Provenance & Evidence