Hydrochloric Acid → HCID 71736385, compound

Participants

Reaction Conditions

Reaction Steps

A resealable tube was charged with a mixture of (S)-3-((R)-4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one and (S)-3-((S)-4-(2-fluoro-5-(pyrimidin-2-yl)pyridin-3-yl)cyclohex-3-en-1-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.090 g, 0.202 mmol), dioxane (3.0 mL), and water (1.0 mL). Concentrated HCl (37%) (0.25 mL) was added, the system was flushed with argon, the tube was sealed, and the reaction mixture was stirred at 100° C. for 2 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution. The aqueous phase was washed and extracted with EtOAc. The combined organic phases were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford an off-white solid. This material was purified via SFC separation (Chiralpak AD-H column (2×15 cm), eluting with 25% MeOH (0.2% DEA)/CO2, 100 bar, 70 mL/min, 220 nM. Injection volume 0.5 mL, 9 mg/mL MeOH) to afford (S)-5,5-dimethyl-3-((S)-4-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)cyclohex-3-en-1-yl)-4-phenyloxazolidin-2-one (0.026 g, 0.059 mmol, 29% yield) as a white solid (first eluting peak, structure arbitrarily assigned). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.82 (s, 3H), 1.50 (s, 3H), 1.86-2.23 (m, 4H), 2.27-2.48 (m, 1H), 2.54-2.70 (m, 1H), 3.56-3.84 (m, 1H), 4.51-4.89 (m, 1H), 6.35 (br. s., 1H), 7.14-7.62 (m, 6H), 8.05-8.36 (m, 2H), 8.67-8.90 (m, 2H), 11.96 (br. s., 1H). m/z (ESI) 443 (M+H)+.

Provenance & Evidence