反应详情

21.0 mg (0.098 mmol) (1-Cyclopropyl-piperidin-4-ylamine-dihydrochloride were dissolved in 3 mL CH3CN and 3 mL water. 82.3 mg (0.98 mmol, 10 equivalents) NaHCO3 were added. Then, a solution of 48.1 mg (0.098 mmol) 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-trichloromethyl-1H-benzoimidazole-5-carboxylic acid methyl ester in 2 mL CH3CN was added and the resulting mixture was stirred vigorously for 3 h under reflux. The mixture was concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (CH3CN/H2O gradient and 0.05% formic acid) to give pure 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-cyclopropyl-piperidin-4-ylcarbamoyl)-1H-benzoimidazole-5-carboxylic acid in form of a colorless amorphous solid. (Under these conditions the methyl ester was hydrolyzed simultaneously!)

1. temperatureunder reflux
2. concentrationThe mixture was concentrated under reduced pressure
3. customThe residue was purified by preparative RP-HPLC (CH3CN/H2O gradient and 0.05% formic acid)