反应详情

DIPEA (200 mg, 1.6 mmol) was added to a stirred solution of {[5-(4-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid (120 mg, 0.45 mmol) (prepared by the method used for the synthesis of Intermediate 30, starting from (4′-fluorophenyl)acetophenone) in DMF (2 mL) followed by HOBt (65 mg, 0.48 mmol) and EDCI.HCl (92 mg, 0.48 mmol). After 2 minutes 3-chloro-5-(piperidin-4-yloxy)-pyridine hydrochloride (0.114 g, 0.00045 mmol) (prepared by method used for the synthesis of Intermediate 15) 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 column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent) to afford 111 mg (55.5% Yield) of 5-(4-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 458, 97.78%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.3 (m, 1H), 8.21 (m, 1H), 8.04 (m, 1H), 7.8 (m, 2H), 7.7 (m, 1H), 7.3 (m, 2H), 7.1 (s, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (m, 2H), 3.7 (m, 1H), 3.4 (m, 1H), 3.2 (m, 1H), 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 by column chromatography (using 60-120 silica gel and 50% ethyl acetate in hexane as eluent)