m-Toluidine → 1-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide

Participants

Reaction Steps

DIPEA (171 mg, 1.32 mmol) was added to a stirred solution of 1-m-Tolyl-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-methylaniline) in DMF (5 mL) followed by HOBt (44 mg, 0.32 mmol) and EDCI (141 mg, 0.73 mmol). After 2 minutes of stirring, 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (prepared according to Step 1 and 5 of the General Scheme) (110 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 the crude solid. The crude solid obtained was purified by recrystallisation from a solvent system (3:7:0.2), EtOAc:hexane:MeOH to afford 100 mg (70.5% Yield) of 1-m-tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 488, 96.08%. 1H NMR (300 MHz, DMSO-d6): δ 9.3 (s, 1H), 8.5 (t, 1H), 7.84 (s, 1H), 7.8 (d, 1H), 7.56-7.44 (m, 2H), 7.38-7.24 (m, 4H), 4.8 (m, 1H), 4.2 (d, 2H), 3.9 (s, 1H), 3.8 (s, 1H), 3.5 (s, 1H), 3.3 (s, 1H), 2.4 (s, 3H), 2.1 (t, 2H), 1.8 (d, 2H).

Provenance & Evidence