1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

Participants

Reaction Steps

DIPEA (200 mg, 1.54 mmol) was added to a stirred solution of 1-morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 4-aminomorpholine) (70 mg, 0.35 mmol) in DMF (5 mL) followed by HOBt (52 mg, 0.38 mmol) and EDCI (170 mg, 0.88 mmol). After 2 minutes of stirring, 2-amino-1-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (125 mg, 0.38 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the precipitate was collected. The solid was purified by recrystallizing from a mixture of 20% ethyl acetate in hexane and MeOH to afford 116 mg (70.3% Yield) of 1-morpholin-4-yl-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]+: 467.15, 96.7%. 1H NMR (300 MHz, DMSO-d6): δ 8.8 (s, 1H), 8.4 (t, 1H), 7.5 (t, 1H), 7.3 (d, 1H), 6.8 (t, 1H), 4.9 (m, 1H), 4.2 (d, 2H), 3.85 (t, 4H), 3.7 (d, 2H), 3.5 (b, 2H), 3.3 (bs, 4H), 2.0 (d, 2H), 1.8 (d, 2H).

Provenance & Evidence