反应详情

A mixture of 36 parts of N-[4-[[(4-fluorophenyl)methyl]amino]-5-pyrimidinyl]-1-(phenylmethyl}-4-piperidineacetamide and 935 parts of phosphoryl chloride was stirred and refluxed for 8 hours. After cooling, the reaction mixture was evaporated. The residue was decomposed in ice water. The whole was treated with a sodium hydroxide solution. The product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was stirred in 2,2'-oxybispropane. The product was filtered off and crystallized from acetonitrile. The product was filtered off and dried, yielding 10.6 parts (30.4%) of 9-[(4-fluorophenyl)methyl]-8-[[1-(phenylmethyl)-4-piperidinyl]methyl]-9H-purine; mp. 136.4° C. (compound 4).

1. temperaturerefluxed for 8 hours
2. temperatureAfter cooling
3. customthe reaction mixture was evaporated
4. additionThe whole was treated with a sodium hydroxide solution
5. extractionThe product was extracted with 4-methyl-2-pentanone
6. customThe extract was dried
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 pure fractions were collected
12. customthe eluent was evaporated
13. stirringThe residue was stirred in 2,2'-oxybispropane
14. filtrationThe product was filtered off
15. customcrystallized from acetonitrile
16. filtrationThe product was filtered off
17. customdried