反应详情

温度

45 °C

n-hexanol (30.8 g) was added to a solution of N, N-carbonyldiimidazole (61.15 g) and dichloromethane (360 ml) at 15-25° C. and stirred for 3 hours. The organic layer was washed with water followed by sodium chloride solution. Distilled off the solvent from the organic layer completely under reduced pressure to get amide compound. Acetonitrile (157.5 ml) was added to the obtained amide compound. This was added to a mixture of ethyl 3-(2-((4-carbamimidoylphenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate mesylate compound of formula-11 (90 g), potassium carbonate (62.5 g), acetonitrile (378 ml) and water (252 ml) at 25-35° C. The reaction mixture was heated to 40-50° C. and stirred for 8 hours. After completion of the reaction, both the organic and aqueous layers were separated; the organic layer was cooled to −5 to +5° C. and stirred for 2 hours. Filtered the precipitated solid washed with acetonitrile and water. The obtained compound was dissolved in a mixture of acetone (270 ml) and acetonitrile (270 ml) at 45-50° C. Cooled the reaction mixture to 25-30° C. and water (360 ml) was added to it. Filtered the obtained solid and dissolved in the mixture of dichloromethane and sodium chloride solution at 35-40° C. Both the organic and aqueous layers were separated; the organic layer was distilled under reduced pressure and then co-distilled with ethyl acetate. The obtained crude compound was dissolved in ethyl acetate (540 ml) by heating it to 70-80° C. and stirred for 30 minutes. Filtered the reaction mixture, the filtrate was cooled to 35-45° C. and ethanol (8 ml) was added to the reaction mixture. The reaction mixture was again cooled to 25-35° C. and stirred for 3 hours. Filtered the precipitated solid and then dried to get pure title compound.

1. customAfter completion of the reaction
2. customboth the organic and aqueous layers were separated
3. temperaturethe organic layer was cooled to −5 to +5° C.
4. stirringstirred for 2 hours
5. filtrationFiltered the precipitated solid
6. washwashed with acetonitrile and water
7. dissolutionThe obtained compound was dissolved in a mixture of acetone (270 ml) and acetonitrile (270 ml) at 45-50° C
8. temperatureCooled the reaction mixture to 25-30° C.
9. additionwater (360 ml) was added to it
10. filtrationFiltered the obtained solid
11. dissolutiondissolved in the mixture of dichloromethane and sodium chloride solution at 35-40° C
12. customBoth the organic and aqueous layers were separated
13. distillationthe organic layer was distilled under reduced pressure
14. customThe obtained crude compound
15. temperatureby heating it to 70-80° C.
16. stirringstirred for 30 minutes
17. filtrationFiltered the reaction mixture
18. temperaturethe filtrate was cooled to 35-45° C.
19. additionethanol (8 ml) was added to the reaction mixture
20. temperatureThe reaction mixture was again cooled to 25-35° C.
21. stirringstirred for 3 hours
22. filtrationFiltered the precipitated solid
23. customdried