反应详情

温度

70 °C

A mixture of 6.1 parts of 1-[5,5-bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamide, 4.3 parts of 2-chloro-N-(2,4,6-trimethyl-3-pyridinyl)acetamide monohydrochloride, 3.7 parts of sodium carbonate and 90 parts of N,N-dimethylformamide was stirred for 15 hours at 70° C. The reaction mixture was filtered, washed with N,N-dimethylformamide and the filtrate was evaporated in vacuo. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (92.5:7.5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanone and 2-propanol. The salt was filtered off, washed twice with 2-propanone and once with 2,2'-oxybispropane and dried overnight at 100°-110° C., yielding 6.58 parts (61.2%) of 3 -(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-N-(2,4,6-trimethyl-3-pyridinyl)-1-piperazineacetamide trihydrochloride, hemihydrate; mp. 224.7° C. (compound 115).

1. filtrationThe reaction mixture was filtered
2. washwashed with N,N-dimethylformamide
3. customthe filtrate was evaporated in vacuo
4. customThe residue was purified by column chromatography over silica gel using
5. additiona mixture of trichloromethane and methanol (92.5:7.5 by volume) as eluent
6. customThe pure fractions were collected
7. customthe eluent was evaporated
8. customThe residue was further purified by column chromatography over silica gel using
9. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
10. customThe pure fractions were collected
11. customthe eluent was evaporated
12. filtrationThe salt was filtered off
13. washwashed twice with 2-propanone and once with 2,2'-oxybispropane
14. customdried overnight at 100°-110° C.