Methanol → HCID 67168742, compound

Participants

Reaction Steps

To 2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (Preparation 131B, Isomer 2, 25 mg, 0.055 mmol) in DMF (1 mL) was added 1-aminocyclopropanecarbonitrile, HCl (9.74 mg, 0.082 mmol), HATU (24.99 mg, 0.066 mmol), and N-methylmorpholine (0.036 mL, 0.329 mmol). The reaction mixture was stirred for 1 h at room temperature. Methanol was added and it was purified by prep HPLC (Phenomenex 21.2×250 mm, Solvent A: 90% water with 10% MeOH and 0.1% TFA, Solvent B: 90% MeOH with 10% water and 0.1% TFA, Gradient: 0% B to 100% B over 30 min, 20 mL/min, 220 nM) to yield N-(1-cyanocyclopropyl)-2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (11 mg, 0.021 mmol, 38.2% yield) as a white solid: product HPLC ret. time=9.96 min (condition G); LC/MS M+1=521.06; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.06 (1H, s), 7.89 (1H, d, J=7.92 Hz), 7.80 (2H, d, J=7.26 Hz), 7.63-7.76 (3H, m), 7.41-7.51 (2H, m), 6.43 (1H, d, J=4.18 Hz), 5.02 (1H, d, J=3.74 Hz), 3.05 (4H, s), 1.46 (2H, q, J=2.79 Hz), 1.07-1.24 (2H, m).

Provenance & Evidence