反应详情

DIPEA (165 mg, 1.3 mmol) was added to a stirred solution of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid (75 mg, 0.36 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 3′-fluoroacetophenone) in DMF (2 mL) followed by HOBt (51 mg, 0.38 mmol) and EDCI.HCl (73 mg, 0.38 mmol). After 2 minutes 2-amino-1-[4-(2-chloro-phenylamino)-piperidin-1-yl]-ethanone hydrochloride (120 mg, 0.36 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. Washing with methanol afforded 76 mg (43.1% Yield) of 5-(3-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 456, 100%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.06 (t, 1H), 7.44 (m, 4H), 7.12 (m, 4H), 6.84 (d, 1H), 6.58 (m, 1H), 4.9 (d, 1H), 4.3 (d, 1H), 4.2 (m, 2H), 3.7 (m, 1H), 3.6 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 1.9 (m, 2H), 1.4 (m, 2H).

1. customprepared by the method
2. extractionextracted with ethyl acetate
3. dry with materialdried over sodium sulfate
4. concentrationThe organic layer was concentrated under reduced pressure
5. customto afford the residue
6. washWashing with methanol