反应详情

DIPEA (110 mg, 0.85 mmol) was added to a stirred solution of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (50 mg, 0.24 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (33 mg, 0.24 mmol) and EDCI.HCl (49 mg, 0.25 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (75 mg, 0.24 mmol) 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 and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford the residue. Recrystallisation using 25% EtOAc in hexane afforded 89 mg (80.9% Yield) of 5-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 457, 90.38%. 1H NMR (300 MHz, DMSO-d6): 613.8 (s, 1H), 8.2 (bs, 1H), 7.9 (t, 1H), 7.1 (m, 7H), 4.61 (m, 1H), 4.4 (d, 2H), 3.7 (m, 2H), 3.3 (m, 2H), 1.9 (m, 2H), 1.5 (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. concentrationThe organic layer was concentrated under reduced pressure
6. customto afford the residue
7. customRecrystallisation