4-Methylmorpholine → HCID 67170576, 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, 35 mg, 0.096 mmol) in DMF (1 mL) was added 4-methylmorpholine (0.064 mL, 0.58 mmol), 2-aminoethylmethylsulfone hydrochloride (27.7 mg, 0.17 mmol), and BOP (77 mg, 0.17 mmol). The reaction mixture was stirred overnight and was then purified by preparative HPLC (Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10-mM ammonium acetate; Gradient: 45-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min). Fractions containing the desired product were combined and dried via centrifugal evaporation to give 2-hydroxy-N-(2-(methylsulfonyl)ethyl)-2-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)acetamide (8.3 mg, 0.018 mmol, 18.4% yield): product HPLC ret. time=2.54 min. (condition F); LC/MS M+1=468; 1H NMR (400 MHz, 1:1 CD3OD and CDCl3) δ ppm 7.87 (1H, d, J=8.36 Hz), 7.67 (2H, d, J=8.14 Hz), 7.40-7.50 (2H, m), 7.31 (2H, d, J=8.36 Hz), 5.06 (1H, s), 3.73 (2H, t, J=6.49 Hz), 3.19-3.30 (2H, m), 2.94 (3H, s), 2.57-2.70 (2H, m), 1.60-1.77 (2H, m), 0.94 (3H, t, J=7.37 Hz).

Provenance & Evidence