反应详情

温度

40 °C

To a solution of cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid (300 mg, 0.70 mmol, 1.0 equiv) in DCM (5 mL) was added triethylamine (142.1 mg, 194.7 μL, 1.39 mmol, 2.0 equiv) and HATU (341.6 mg, 0.90 mmol, 1.3 equiv) and the mixture stirred at 40° C. After 15 min, trans-4-amino-cyclohexanol hydrochloride (137.04 mg, 0.90 mmol, 1.3 equiv; [CAS RN 50910-54-8]) was added and stirring continued at 50° C. for 2 h. Removal of the solvent mixture under reduced pressure and purification by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate yielded 0.33 g (90%) of the title compound. MS (ES+): 529 (M+H).

1. stirringstirring
2. waitcontinued at 50° C. for 2 h
3. customRemoval of the solvent mixture
4. customunder reduced pressure and purification by silica column chromatography
5. washeluting with a gradient of heptane/ethyl acetate