反应详情

N,N'-carbodiimidazole (0.431 g) was added at a time to a solution of 0.400 g of 6-carboxy-1-(2-chlorobenzyl)-2-methylbenzimidazole in 15 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 1 hour. Subsequently, a solution of 0.498 g of 4-methoxybenzenesulfonamide and 0.405 g of diazabicycloundecene in 5 ml of N,N-dimethylformamide was added thereto, and the mixed solution was stirred at 100° C. for 67 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. Water and chloroform were added to the residue, and 10% hydrochloric acid was added thereto while being cooled until the aqueous layer was acidified. The resulting mixture was extracted twice with chloroform. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, and the solvent was distilled off under reduced pressure. The residue was purified through silica-gel column chromatography (eluent: a mixture of chloroform and methanol at a ratio of 100:2 to 100:10). The resulting product was concentrated, and was crystallized from a mixed solution of ethyl acetate and diethyl ether. The crystals were separated through filtration, and were dried to give 0.450 g of 1-(2-chlorobenzyl)-6-(4-methoxybenzenesulfonylcarbamoyl)-2-methylbenzimidazole (217).

1. stirringthe mixed solution was stirred at 100° C. for 67 hours
2. temperatureThe reaction solution was cooled
3. distillationthe solvent was distilled off under reduced pressure
4. additionWater and chloroform were added to the residue, and 10% hydrochloric acid
5. additionwas added
6. temperaturewhile being cooled until the aqueous layer
7. extractionThe resulting mixture was extracted twice with chloroform
8. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate
9. distillationthe solvent was distilled off under reduced pressure
10. customThe residue was purified through silica-gel column chromatography (eluent
11. additiona mixture of chloroform and methanol at a ratio of 100:2 to 100:10)
12. concentrationThe resulting product was concentrated
13. customwas crystallized from a mixed solution of ethyl acetate and diethyl ether
14. customThe crystals were separated through filtration
15. customwere dried