反应详情

A mixture of 8.7 parts of (1,1-dimethylethyl) [[4-[[2-[2-(aminocarbonyl)-4-[5,5bis(4-fluorophenyl)pentyl]-1-piperazinyl]acetyl]amino]-3,5-dichlorophenyl]methyl]carbamate, 120 parts of methanol and 24 parts of 2-propanol, saturated with hydrogen chloride was stirred for 30 minutes at reflux temperature. The reaction mixture was evaporated and the residue was taken up in water. The whole was treated with an ammonium hydroxide solution and the product was extracted twice with dichloromethane. The combined extracts were washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (93:7 by volume) as eluent. The desired fraction was collected and the eluent was evaporated. The residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 3.34 parts (44.9%) of 2-(aminocarbonyl)-N-[4-(aminomethyl)-2,6-dichlorophenyl]-4-[5,5-bis(4-fluorophenyl)pentyl]-1-piperazineacetamide; mp. 160.8° C. (compound 100).

1. temperatureat reflux temperature
2. customThe reaction mixture was evaporated
3. additionThe whole was treated with an ammonium hydroxide solution
4. extractionthe product was extracted twice with dichloromethane
5. washThe combined extracts were washed with water
6. customdried
7. filtrationfiltered
8. customevaporated
9. customThe residue was purified by column chromatography over silica gel using
10. additiona mixture of trichloromethane and methanol
11. customThe desired fraction was collected
12. customthe eluent was evaporated
13. filtrationThe product was filtered off
14. customdried