反应详情

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (0.0576 g, 0.00021 mol) in DMF (1 mL), was added DIPEA (0.1317 g, 0.0010 mol), HOBt (0.035 g, 0.00025 mol) and EDCI.HCl (0.049 g, 0.00025 mol) at ambient temperature. After 2 minutes methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride (0.06 g, 0.00021 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product extracted with ethyl acetate. The ethyl acetate layer was collected and washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B), gradient: (Time): (% B)-0:30; 2:50; 8:80)]) to afford 0.015 g (15%) of 5-phenyl-isoxazole-3-carboxylic acid (2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 487.19 (M+1)+, 98.16%, 1H NMR (DMSO-d6): δ 8.58 (t, 1H), 7.94 (m, 2H), 7.7 (m, 2H), 7.56 (m, 3H), 7.34 (m, 2H), 4.3 (m, 1H), 4.15 (d, 2H), 3.8 (d, 1H), 3.0 (m, 2H), 2.6 (s, 3H), 1.7 (m, 2H), 1.4 (m, 1H), 1.3 (m, 2H).

1. extractionthe product extracted with ethyl acetate
2. customThe ethyl acetate layer was collected
3. washwashed with brine solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B)