1,2-Dichloroethane → N-[(1R)-1-(5-Fluoro-1-oxidopyridin-2-yl)ethyl]-3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzamide

Participants

Reaction Steps

To a solution of 3-(5-methylpyridin-2-yl)-5-[(5S)-5-pyridin-2-yl-4,5-dihydroisoxazol-3-yl]benzoic acid (50.0 mg, 0.12 mmol) in N,N-dimethylformamide (1 mL) were added (1R)-1-(5-fluoro-1-oxidopyridin-2-yl)ethanamine hydrochloride salt (33.4 mg, 0.17 mmol), EDC (33.3 mg, 0.17 mmol), HOAT (7.9 mg, 0.06 mmol) and triethylamine (0.11 mL, 0.81 mmol). The reaction mixture was stirred at ambient temperature for 1.5 h. The reaction mixture was heated to 50° C. After 20 min, the mixture was cooled to ambient temperature and the solid in the reaction was filtered off. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→65% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (46 mg). HRMS 498.1954 (M+1). 1H NMR (400 MHz, CDCl3): δ 8.56 (d, J=4.8 Hz, 1H); 8.48 (s, 1H); 8.46-8.35 (m, 3H); 8.15-8.08 (m, 2H); 7.73-7.65 (m, 2H); 7.54 (t, J=8.9 Hz, 2H); 7.34 (t, J=7.8 Hz, 1H); 7.20 (dd, J=7.7, 4.8 Hz, 1H); 7.06 (ddd, J=8.8, 6.6, 2.4 Hz, 1H); 5.86 (dd, J=10.9, 6.9 Hz, 1H); 5.58-5.48 (m, 1H); 3.92-3.74 (m, 2H); 2.35 (s, 3H); 1.70 (d, J=7.0 Hz, 3H).

Provenance & Evidence