反应详情

DIPEA (190 mg, 1.47 mmol) was added to a stirred solution of 1-cyclopropyl-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from cyclopropylamine) (50 mg, 0.32 mmol) in DMF (5 mL) followed by HOBt (48 mg, 0.35 mmol) and EDCI (156 mg, 0.81 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (127 mg, 0.37 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was added and the solid precipitate was filtered. The solid was purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent) to afford 94 mg (56.62% Yield) of 4-(2-oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide. LC/MS [M+H]+: 490.19, 98.95%. 1H NMR (300 MHz, DMSO-d6): δ 8.6 (t, 1H), 7.94 (d, 2H), 7.8 (d, 2H), 7.6 (t, 1H), 7.38 (t, 3H), 4.8 (m, 1H), 4.2 (d, 1H), 4.0 (t, 3H), 3.8 (d, 1H), 3.5 (d, 1H), 3.3 (bs, 1H), 2.5 (bs, 2H), 2.1 (m, 2H), 2.0 (d, 2H), 1.7 (d, 2H).

1. customprepared by the method
2. additionwas added
3. stirringthe resulting mixture was stirred at room temperature overnight
4. filtrationthe solid precipitate was filtered
5. customThe solid was purified by column chromatography (using 60-120 silica gel and 70% ethyl acetate in hexane as eluent)