反应详情

To a stirred solution of (4-phenylamino-benzoylamino)-acetic acid (0.051 g, 0.00019 mol) in DMF (5 mL) was added DIPEA (0.061 g, 0.00048 mol), HOBt (0.025 g, 0.00019 mol) and EDCI.HCl (0.076 g, 0.00040 mol) at ambient temperature. After 2 minutes methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride (0.047 g, 0.00016 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 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 0.031 (38%) of N-(2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide. LCMS: 511.22 (M+1)+, 99.08%, 1H NMR (DMSO-d6): δ 8.6 (s, 1H), 8.2 (t, 1H), 7.8 (d, 2H), 7.7 (m, 3H), 7.4 (m, 3H), 7.2 (d, 2H), 7.1 (d, 2H), 6.9 (t, 1H), 4.4 (d, 1H), 4.1 (d, 2H), 3.9 (d, 1H), 3.1 (m, 3H), 2.6 (s, 4H), 1.8 (d, 2H), 1.4 (m, 1H).

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 residue was purified by preparative HPLC [(column-Zorbax SB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/Acetonitrile (B)