3-(Trifluoromethyl)aniline → 1-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Participants

Reaction Steps

1-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acid (280 mg, 0.87 mmol), HATU (328 mg, 0.86 mmol), DMF (1.5 mL) and DIEA (0.5 mL, 3.87 mmol) were combined and vortexed until a homogeneous mixture was obtained. 3-Trifluoromethyl-phenylamine (0.109 mL, 0.87 mmol) was added and the resulting mixture stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with sat'd NaHCO3 (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by column chromatography (4:1 hexanes:EtOAc, followed by 1:1 hexanes:EtOAc) to give 100 mg (25%) of 1-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperidine-4-carboxylic acid (3-trifluoromethyl-phenyl)-amide as a white solid after lyophilization from H2O—AcCN. 1H NMR (CD3OD) 8.54 (d, 2H), 8.02 (s, 1H), 7.74 (d, 1H), 7.51-7.46 (m, 3H), 7.36 (d, 1H), 5.57 (s, 2H), 4.32 (m, 2H), 3.00 (m, 2H), 2.64 (m, 1H), 1.96-1.90 (m, 4H) ppm. LC-MS (MH+)=464.

Provenance & Evidence