Ammonia → HCID 58020095, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled (0-5° C.) and stirred solution of (S)-1-[5-(3′-chloro-2-fluoro-6methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-azetidine-2-carboxylic acid (I-143, 0.22 g, 0.54 mmol) in THF (2.5 mL) was added N,N-diisopropylethylamine (0.07 g, 0.57 mmol). The reaction mixture was stirred for 5 min, isobutylchloroformate (0.08 g, 0.57 mmol) was added, stirred at 0-5° C. for 45 min. Ammonia in methanol (7M sol, 1.0 mL, 7.0 mmol) was added, the reaction warmed to room temperature, and stirred for 0.5 h. The reaction mixture was diluted with water (5 mL). The organic layer was separated, the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using 5% methanol in dichloromethane, followed by preparative thin layer chromatography using 5% methanol in dichloromethane to afford 0.06 g (27%) of P-615 as an off-white solid. 1H NMR (DMSO-d6, 400 MHz): 7.99 (d, J=2.8 Hz, 1H), 7.51 (br s, 1H), 7.34-7.46 (m, 4H), 7.24-7.3 (m, 2H), 7.14 (br s, 1H), 6.92 (d, J=8.4 Hz, 1H), 6.35 (d, J=8.4 Hz, 1H), 4.39 (dd, J=9.6, 6.8 Hz, 1H), 3.7-3.9 (m, 2H), 3.8 (s, 2H), 3.72 (s, 3H), 2.26-2.48 (m, 2H) ppm;

Provenance & Evidence