反应详情

温度

10 °C

HOBt (25 mg, 0.185 mmol) and DIPEA (22 mg, 0.175 mmol) were added to a stirred solution of N-biphenyl-4-yl-malonamic acid (50 mg, 0.175 mmol) in DMF (3 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (50 mg, 0.26 mmol) followed by (2-trifluoromethyl-5-fluoro-phenyl)-piperazin-1-yl-methanone hydrochloride (60 mg, 0.193 mmol) were added. The reaction mixture was stirred at room temperature overnight. Water was then added and the resulting precipitate was filtered. The solid was purified by column chromatography using silica gel 60-120 mesh and 40% ethyl acetate in hexane as eluant to afford 34 mg (38%) of N-biphenyl-4-yl-3-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-3-oxo-propionamide. LCMS: 514.17M+1)+, 95.5%. 1H NMR: (CDCl3): δ 9.6 (d, 1H), 7.75 (m, 1H), 7.6 (m, 6H), 7.44 (t, 2H), 7.35 (t, 1H), 7.2 (m, 1H), 7.06 (m, 1H), 4.0 (m, 2H), 3.7 (m, 4H), 3.56 (s, 2H), 3.48 (s, 1H), 3.26 (m, 3H).

1. additionwere added
2. filtrationthe resulting precipitate was filtered
3. customThe solid was purified by column chromatography