反应详情

温度

40 °C

A mixture of 3-(2,4-dichlorobenzyl)-2-methyl-3H-benzimidazole-5-carboxylic acid (34.1 g, 102 mmol), N,N′-carbonyldiimidazole (21.4 g) and N,N-dimethylformamide (122.7 g) was stirred for one hour at 35° C., into which 1-pentanesulfonamide (20.0 g) and 1,8-diazabicyclo[5.4.0]-7-undecene (20.1 g) were then added, and stirred for 6 hours at 40° C. After the reaction, a portion of N,N-dimethylformamide (62.9 g) was distilled off in vacuo, and, to the residue were added methanol (227.8 g) and water (227.8 g). This solution contained 1,8-diazabicyclo[5.4.0]-7-undecene and imidazole generated from N,N′-carbonyldiimidazole as the bases. This solution was filtered to remove insoluble materials, and the filtrate was heated to 50° C., and conc. hydrochloric acid (20.4 g) was added drop-wise thereto over one hour. After the dropping, crystal form B of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide (119 mg) was added as seed crystal, and the mixture was allowed to be ripen for 2 hours. After the ripening, conc. hydrochloric acid (15.5 g) was further added drop-wise thereto over 2 hours. The slurry was ripened for one hour at 50° C. and cooled down to 30° C., and then the crystals were collected by filtration. The crystals were washed with a mixed solvent of methanol (120 g) and water (120 g), and vacuum-dried to obtain crystal form B of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide.

1. additionwere then added
2. customAfter the reaction
3. distillationa portion of N,N-dimethylformamide (62.9 g) was distilled off in vacuo
4. additionto the residue were added methanol (227.8 g) and water (227.8 g)
5. filtrationThis solution was filtered
6. customto remove insoluble materials
7. temperaturethe filtrate was heated to 50° C.
8. additionconc. hydrochloric acid (20.4 g) was added drop-wise
9. waitover one hour
10. additionAfter the dropping, crystal form B of 3-(2,4-dichlorobenzyl)-2-methyl-N-(pentylsulfonyl)-3H-benzimidazole-5-carboxamide (119 mg) was added as seed crystal
11. waitto be ripen for 2 hours
12. additionAfter the ripening, conc. hydrochloric acid (15.5 g) was further added drop-wise
13. waitover 2 hours
14. waitThe slurry was ripened for one hour at 50° C.
15. temperaturecooled down to 30° C.
16. filtrationthe crystals were collected by filtration
17. washThe crystals were washed with a mixed solvent of methanol (120 g) and water (120 g)
18. customvacuum-dried