反应详情

A mixture of 7.6 parts of 5-chloro-1,3-dihydro-1-(3-hydroxypropyl)-2H-benzimidazol-2-one methanesulfonate, 5.5 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 5 parts of sodium carbonate and 63 parts of N,N-dimethylformamide is stirred and heated in an oil-bath at 50°-60° C. for 2 hours. The reaction mixture is poured onto water. The precipitated product is filtered off, dried and purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The solid residue is crystallized from 4-methyl-2-pentanone. The product is filtered off and recrystallized from a mixture of N,N-dimethylformamide and water. It is filtered off again and dissolved in a mixture of 4-methyl-2-pentanone and a small amount of N,N-dimethylformamide. The solution is filtered till clear and the filtrate is concentrated to a volume of about 10 parts. The concentrate is triturated in methanol. The precipitated product is filtered off and dried, yielding 1.27 parts of 5-chloro-1-{3-[4-(5-chloro-1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 229°-236° C.

1. temperatureheated in an oil-bath at 50°-60° C. for 2 hours
2. additionThe reaction mixture is poured onto water
3. filtrationThe precipitated product is filtered off
4. customdried
5. custompurified by column-chromatography over silica gel using
6. additiona mixture of trichloromethane and 10% of methanol as eluent
7. customThe pure fractions are collected
8. customthe eluent is evaporated
9. customThe solid residue is crystallized from 4-methyl-2-pentanone
10. filtrationThe product is filtered off
11. customrecrystallized from a mixture of N,N-dimethylformamide and water
12. filtrationIt is filtered off again
13. dissolutiondissolved in a mixture of 4-methyl-2-pentanone
14. filtrationThe solution is filtered till clear and the filtrate
15. concentrationis concentrated to a volume of about 10 parts
16. customThe concentrate is triturated in methanol
17. filtrationThe precipitated product is filtered off
18. customdried