3-Fluoroaniline → 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

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Reaction Steps

DIPEA (168 mg, 1.3 mmol) was added to a stirred solution of 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid (60 mg, 0.29 mmol) (prepared by the method used for the synthesis of Intermediate 64, starting from 3-fluoroaniline) in DMF (5 mL) followed by HOBt (43 mg, 0.32 mmol) and EDCI (139 mg, 0.72 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (103 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. Cold water was then added and the solid was collected to afford 128 mg (92.75% Yield) of 1-(3-fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 476, 96.08%. 1H NMR (300 MHz, DMSO-d6): δ 9.4 (s, 1H), 8.54 (t, 1H), 8.0-7.96 (t, 2H), 7.72 (q, 1H), 7.54-7.34 (m, 2H), 7.34 (d, 1H), 6.9 (t, 1H), 4.9 (s, 1H), 4.3 (d, 2H), 3.8 (bs, 2H), 3.55 (bs, 2H), 2.05 (d, 2H), 1.8 (d, 2H).

Provenance & Evidence