反应详情

To 2.2 g of 5-amino-1-[3-(1-isopropyl-5-tetrazolyl)propyl]indole was added 40 ml of toluene, then this mixture was stirred under nitrogen gas atmosphere by cooling in a methanol-ice bath. To this reaction mixture was added 4 ml of n-hexane solution of 2M trimethylaluminum dropwise from syringe, then reaction mixture was stirred for 20 minutes, and further stirred at room temperature for 1 hour. 2.18 Grams of methyl 1-benzyl-6-chlorobenzimidazol-2-carboxylate was added to the reaction mixture and was stirred for 5 to 6 hours under refluxing condition. Next, 10% hydrochloric acid was added, and the crystals being separated were collected by filtration. Water-chloroform was added to the crystals, this solution was made alkaline with 10% aqueous solution of potassium hydroxide, then was filtered with Celite, the chloroform layer was washed with water, an aqueous solution saturated with sodium chloride. The chloroform layer was dried with anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue thus obtained was subjected to a silica gel column chromatography (eluent: 3% methanol/dichloromethane), and recrystallized from ethyl acetate-n-hexane, there was obtained 2.27 g of 1-benzyl-6-chloro-2-{1-[3-(1-isopropyltetrazol-5-yl)propyl]indol-5-ylaminocarbonyl}benzimidazole as in the form of yellow needle crystals.

1. temperatureby cooling in a methanol-ice bath
2. customreaction mixture
3. stirringwas stirred for 20 minutes
4. stirringfurther stirred at room temperature for 1 hour
5. stirringwas stirred for 5 to 6 hours
6. temperatureunder refluxing condition
7. customthe crystals being separated
8. filtrationwere collected by filtration
9. additionWater-chloroform was added to the crystals
10. filtrationwas filtered with Celite
11. washthe chloroform layer was washed with water
12. dry with materialThe chloroform layer was dried with anhydrous magnesium sulfate
13. customthe solvent was removed under reduced pressure
14. customThe residue thus obtained
15. customrecrystallized from ethyl acetate-n-hexane