4-Methylmorpholine → HCID 86669940, compound

Participants

Reaction Steps

To a solution of 2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetic acid (Example 127, 20 mg, 0.055 mmol) in DMF (1 mL) was added 4-methylmorpholine (0.036 mL, 0.33 mmol), 2-aminoacetonitrile (5.55 mg, 0.1 mmol) and BOP (43.8 mg, 0.1 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (Phenomenex Luna 5 u C18 21.2×100 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 10 min, 20 mL/min, 220 nM, product retention time=11.9 min) to give N-(cyanomethyl)-2-hydroxy-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (11.2 mg, 0.026 mmol, 46.9% yield): product HPLC ret. time=9.89 min. (condition G); LC/MS M+1=402.1; 1H NMR (400 MHz, CD3OD) δ ppm 7.88 (1H, d, J=7.92 Hz), 7.72 (2H, d, J=8.36 Hz), 7.43-7.53 (2H, m), 7.37 (2H, d, J=8.36 Hz), 5.13 (1H, s), 4.19 (2H, d, J=1.76 Hz), 3.06 (4H, s), 2.67 (2H, t, J=7.59 Hz), 1.62-1.77 (2H, m), 0.97 (3H, t, J=7.37 Hz).

Provenance & Evidence