反应详情

To a stirred solution of [(5-phenyl-isoxazole-3-carbonyl)-amino]-acetic acid (0.075 g, 0.00027 mol) in DMF (2 mL), was added DIPEA (171.5 mg, 0.00133 mol), HOBt (44.8 mg, 0.00033 mol) and EDCI.HCl (0.064 g, 0.00033 mol) at ambient temperature. After 2 minutes (2-bromo-phenyl)-piperidin-4-yl-amine dihydrochloride (0.078 g, 0.00026 mol) was added and the resulting mixture was stirred overnight. The reaction mixture was then diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using basic aluminium oxide (35% ethyl acetate in hexane) to afford 0.028 g (22%) of 5-phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 483.1 (M+1)+, 97.4%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 7.85 (m, 2H), 7.6 (m, 3H), 7.4 (m, 2H), 7.2 (t, 1H), 6.85 (d, 1H), 6.55 (t, 1H), 4.7 (d, 1H), 4.3 (d, 1H), 4.2 (d, 2H), 3.9 (d, 1H), 3.6 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.0 (t, 2H), 1.4 (m, 2H).

1. extractionthe product was extracted with ethyl acetate
2. washThe ethyl acetate layer was washed with brine solution
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customThe resulting residue was purified by column chromatography