反应详情

A mixture of 5 parts of 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride, 5 parts of 3-(1-piperazinyl)-1,2-benzisothiazole dihydrochloride, 8 parts of sodium carbonate, 0.2 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone was stirred for 20 hours at reflux temperature. The reaction mixture was filtered and the filtrate was 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 converted into the (E)-2-butenedioate salt in 2-propanol. The salt was filtered off and crystallized from ethanol. The product was filtered off and dried, yielding 7.4 parts (85%) of 3-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one (E)-2-butenedioate(1:1); mp. 186.0° C. (compound 1).

1. temperatureat reflux temperature
2. filtrationThe reaction mixture was filtered
3. customthe filtrate was evaporated
4. customThe residue was purified by column chromatography over silica gel using
5. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
6. customThe pure fractions were collected
7. customthe eluent was evaporated
8. filtrationThe salt was filtered off
9. customcrystallized from ethanol
10. filtrationThe product was filtered off
11. customdried