反应详情

温度

50 °C

To a stirred and cooled (0° C.) mixture of 3.8 parts of poly(oxymethylene) 37%, 15.5 parts of 1-[(4-fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine and 7 parts of glacial acetic acid were added 6.5 parts of 2-methylimidazo[1,2-a]pyridine under nitrogen atmosphere. The whole was heated slowly to 50° C. and stirring was continued at 50° C. for 2 hours. After stirring was continued overnight at room temperature, the reaction mixture was poured into water and the whole was made alkaline with sodium hydroxide. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 6.7 parts (30%) of 1-[(4-fluorophenyl)methyl]-N-[(2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-4-piperidinyl]-1H-benzimidazol-2-amine; mp. 198.1° C. (compound 106).

1. temperaturecooled
2. stirringstirring
3. stirringAfter stirring
4. waitwas continued overnight at room temperature
5. extractionThe product was extracted with dichloromethane
6. customThe extract was dried
7. filtrationfiltered
8. customevaporated
9. customThe residue was purified by column chromatography over silica gel using
10. additiona mixture of trichloromethane and methanol
11. customThe pure fractions were collected
12. customthe eluent was evaporated
13. customThe residue was crystallized from acetonitrile
14. filtrationThe product was filtered off
15. customdried