反应详情

N,N′-carbonyldiimidazole (0.431 g) is added all at once to an N,N-dimethylformamide (15 ml) solution of 6-carboxy-1-(2-chlorobenzyl)-2-methylbenzimidazole (0.400 g) (example 75), and the solution is stirred for one hour at room temperature. Subsequently, an N,N-dimethylformamide (5 ml) solution of 4-methoxybenzenesulfonamide (0.498 g) and diazabicycloundecene (0.405 g) is added, and the solution is stirred for 67 hours at 100° C. The reaction solution is cooled and the solvent is removed through evaporation under reduced pressure. Water and chloroform are added to the residue. While being stirred, 10% hydrochloric acid is added until the aqueous layer became acidic. The organic layer, which is obtained through chloroform extraction (twice), is washed with a saturated sodium bicarbonate aqueous solution, and the solvent is removed through evaporation under reduced pressure. After purification using silica gel column chromatography (eluate: chloroform/methanol=100/2˜100/10) and then concentration, crystals are formed in a mixture solution of ethyl acetatc and diethylether. The crystals are separated through filtration, dried, and thus, 1-(2-chlorobenzyl)-6-(4-methoxybenzenesulfonylcarbamoyl)-2-methylbenzimidazole (0.450 g) is obtained.

1. stirringthe solution is stirred for 67 hours at 100° C
2. temperatureThe reaction solution is cooled
3. customthe solvent is removed through evaporation under reduced pressure
4. additionWater and chloroform are added to the residue
5. stirringWhile being stirred
6. addition10% hydrochloric acid is added until the aqueous layer
7. customThe organic layer, which is obtained through chloroform extraction (twice),
8. washis washed with a saturated sodium bicarbonate aqueous solution
9. customthe solvent is removed through evaporation under reduced pressure
10. customAfter purification
11. concentrationconcentration, crystals
12. customare formed in a mixture solution of ethyl acetatc and diethylether
13. customThe crystals are separated through filtration
14. customdried