反应详情

N,N′-carbonyldiimidazole (0.324 g) was added to a solution of 6-carboxy-1-(isoquinolin-3-ylmethyl)-2-methylbenzimidazole (0.413 g) as obtained in Production Example 5 in N,N-dimethylformamide (10 ml) all at once and the mixture was stirred at room temperature for 1.5 hour. Then, 1-pentanesulfonamide (0.302 g) and diazabicyclo-undecene (0.304 g) were added thereto, and the resulting mixture was stirred at 100° C. for 6.5 hour. The reaction solution was concentrated, brine was added to the concentrate, and the mixture was extracted with chloroform. The organic layer was concentrated and the residue was purified by silica gel column chromatography (eluate: methanol/chloroform=1/19) followed by recrystallization from hexane/ethyl acetate (2/3) to yield the desired compound, 1-(isoquinolin-3-ylmethyl)-2-methyl-6-(1-pentanesulfonyl-carbamoyl)benzimidazole (13) (0.142 g).

1. stirringthe resulting mixture was stirred at 100° C. for 6.5 hour
2. concentrationThe reaction solution was concentrated
3. additionbrine was added to the concentrate
4. extractionthe mixture was extracted with chloroform
5. concentrationThe organic layer was concentrated
6. customthe residue was purified by silica gel column chromatography (eluate: methanol/chloroform=1/19)
7. customfollowed by recrystallization from hexane/ethyl acetate (2/3)