反应详情

DIPEA (131 mg, 1.0 mmol) was added to a stirred solution of 5-(4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (60 mg, 0.29 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 4′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (41 mg, 0.305 mmol) and EDCI.HCl (59 mg, 0.306 mmol). After 2 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (98 mg, 0.294 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure The residue was purified by washing with 1% MeOH in EtOAc to afford 97 mg (68.3% Yield) of 5-(4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 491, 92.85%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.1 (t, 1H), 7.9 (m, 2H), 7.5 (t, 1H), 7.24 (m, 5H), 7.1 (d, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 2H), 2.0 (m, 2H), 1.6 (m, 2H).

1. customprepared by the method
2. additionwas added to the reaction mixture
3. extractionextracted with ethyl acetate
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated under reduced pressure The residue
6. customwas purified
7. washby washing with 1% MeOH in EtOAc