1-Hydroxybenzotriazole → 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

関与物質

反応手順

DIPEA (120 mg, 0.98 mmol) was added to a stirred solution of {[5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carbonyl]-amino}-acetic acid (80 mg, 0.28 mmol) (prepared by the method used for the synthesis of Intermediate 30, starting from 2-acetyl-5-chlorothiophene) in DMF (2 mL) followed by HOBt (40 mg, 0.29 mmol) and EDCI.HCl (56 mg, 0.29 mmol). After 5 minutes 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (70 mg, 0.28 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. Purification by recrystallisation from 10% EtOAc in hexane afforded 84 mg (65.1% Yield) of 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 481, 90.38%. 1H NMR (300 MHz, DMSO-d6): δ 13.6 (s, 1H), 8.6 (m, 1H), 7.18 (m, 4H), 7.1 (m, 1H), 6.8 (m, 1H), 4.7 (m, 1H), 4.2 (d, 2H), 3.8 (m, 1H), 3.7 (m, 1H), 1.9 (m, 2H), 1.6 (m, 2H).

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