1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-phenyl-1H-pyrazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

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Reaction Steps

DIPEA (223 mg, 0.3 mL, 1.72 mmol) was added to a stirred solution of 1-phenyl-1H-pyrazole-4-carboxylic acid (65 mg, 0.34 mmol) in DMF (5 mL) followed by HOBt (51 mg, 0.38 mmol) and EDCI (165 mg, 0.86 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride salt (116 mg, 0.38 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (using 60-120 silica gel and 70% EtOAc in hexane as eluent) to afford 70 mg (46.35% yield) of 1-phenyl-1H-pyrazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 439.15, 95.23%. 1H NMR (300 MHz, CDCl3): δ 8.4 (s, 1H), 8.06 (s, 1H), 7.76 (d, 2H), 7.54 (t, 2H), 7.42 (m, 2H), 7.2 (d, 1H), 7.1 (t, 1H), 7.0 (t, 2H), 4.7 (t, 1H), 4.4-4.2 (m, 2H), 4.1 (m, 1H), 3.8-3.5 (m, 2H), δ 3.5 (m, 1H), 2.1-1.8 (m, 4H).

Provenance & Evidence