反应详情

A mixture of 1.9 parts of 2-chlorobenzothiazole, 3.7 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 22.5 parts of methylbenzene was stirred and refluxed overnight. 1.6 Parts of sodium carbonate were added and the whole was stirred for 4 hours at reflux temperature. The methylbenzene layer was washed with water and set aside. The precipitated product, which was formed during the reaction, was filtered off and dissolved in trichloromethane. The solution was washed with water. The combined organic layers (trichloromethane and methylbenzene layers) were 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 acetonitrile. The product was filtered off and dried, yielding 2.06 parts (41.2%) of cis-4-amino-N-[1-[3-(2-benzothiazolylamino)propyl]-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide; mp. 161.5° C. (compound 45).

1. temperaturerefluxed overnight
2. stirringthe whole was stirred for 4 hours
3. temperatureat reflux temperature
4. washThe methylbenzene layer was washed with water
5. customThe precipitated product, which was formed during the reaction
6. filtrationwas filtered off
7. dissolutiondissolved in trichloromethane
8. washThe solution was washed with water
9. dry with materialThe combined organic layers (trichloromethane and methylbenzene layers) were dried
10. filtrationfiltered
11. customevaporated
12. customThe residue was purified by column chromatography over silica gel using
13. additiona mixture of trichloromethane and methanol
14. customThe pure fractions were collected
15. customthe eluent was evaporated
16. customThe residue was crystallized from acetonitrile
17. filtrationThe product was filtered off
18. customdried