反应详情

To a stirred mixture of 4.28 parts of cis-4-amino-N-[1-(2-aminoethyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide, 1.21 parts of N,N-diethylethanamine and 150 parts of trichloromethane was added a solution of 1.5 parts of 2-chloropyrimidine in 75 parts of trichloromethane. The whole was stirred and refluxed for 80 hours. After cooling, the reaction mxiture was poured into a saturated sodium carbonate solution. The product was extracted with trichloromethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (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 1.52 parts (29.2%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]benzamide monohydrate; mp. 123.5° C. (compound 46).

1. temperaturerefluxed for 80 hours
2. temperatureAfter cooling
3. extractionThe product was extracted with trichloromethane
4. washThe extract was washed with water
5. customdried
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by column chromatography over silica gel using
9. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
10. customThe pure fractions were collected
11. customthe eluent was evaporated
12. customThe residue was crystallized from acetonitrile
13. filtrationThe product was filtered off
14. customdried