反应详情

1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine, dihydrochloride salt (2.13 g, 6.1 mmol), dichloromethane (40 mL), and triethylamine (2.5 mL, 17.9 mmol) were combined and cooled in an icebath. 1-Isocyanato-3,5-bis-trifluoromethyl-benzene (1.89 g, 7.4 mmol) in dichloromethane (10 mL) was added dropwise and the resulting mixture stirred overnight at room temperature. 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 (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc) to give 2.6 g (80%) of 4-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide as a white solid after lyophilization from: H2O—AcCN. 1H NMR (CDCl3) 8.62 (d, 2H), 7.84 (s, 2H), 7.50 (s, 1H), 7.31 (d, 2H), 7.06 (s, 1H), 5.49 (s, 2H), 3.68-3.60 (m, 8H) ppm. LC-MS (MH+)=533.

1. temperaturecooled in an icebath
2. washwashed with sat'd NaHCO3 (3×), sat'd NaCl (1×)
3. dry with materialdried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc)