反应详情

温度

60 °C

A mixture of 2 parts of 2-bromothiazole and 4.28 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide was stirred for one hour at 60° C. Ths mixture solidified. It was suspended in 10 parts of pyridine and stirring was continued overnight at reflux. The reaction mixture was evaporated. The residue was taken up in a saturated sodium carbonate solution. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (93:7 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanol. The salt was filtered off and the free base was liberated in the conventional manner and extracted with trichloromethane. 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, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of acetonitrile and 2,2'-oxybispropane. The product was filtered off and dried, yielding 0.6 parts (11%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(2-thiazolylamino)ethyl]-4-piperidinyl]benzamide; mp. 140.9° C. (compound 44).

1. stirringstirring
2. waitwas continued overnight
3. temperatureat reflux
4. customThe reaction mixture was evaporated
5. extractionThe product was extracted with trichloromethane
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 (93:7 by volume) as eluent
11. customThe pure fractions were collected
12. customthe eluent was evaporated
13. filtrationThe salt was filtered off
14. extractionextracted with trichloromethane
15. customThe extract was dried
16. filtrationfiltered
17. customevaporated
18. customThe residue was purified by column chromatography over silica gel using
19. additiona mixture of trichloromethane and methanol
20. customThe pure fractions were collected
21. customthe eluent was evaporated
22. customThe residue was crystallized from a mixture of acetonitrile and 2,2'-oxybispropane
23. filtrationThe product was filtered off
24. customdried