反应详情

A mixture of 1.56 parts of 2-(methylthio)-4-pyrimidinol, 3.7 parts of cis-4-amino-N-[1-(3-aminopropyl)-3-methoxy-4-piperidinyl]-5-chloro-2-methoxybenzamide and 64 parts of acetonitrile was stirred for 40 hours at reflux temperature. Another portion of 0.7 parts of 2-(methylthio)-4-pyrimidinol was added and stirring was continued over weekend at reflux temperature. The reaction mixture was evaporated. The residue was taken up in trichloromethane. The whole was washed with water, saturated with ammonium hydroxide, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (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 1.82 parts (39.5%) of cis-4-amino-5-chloro-N-[1-[3-[(4-hydroxy-2-pyrimidinyl)amino]propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide monohydrate; mp. 134.2° C. (compound 42).

1. temperatureat reflux temperature
2. stirringstirring
3. waitwas continued over weekend
4. temperatureat reflux temperature
5. customThe reaction mixture was evaporated
6. washThe whole was washed with water, saturated with ammonium hydroxide
7. customdried
8. filtrationfiltered
9. customevaporated
10. customThe residue was purified by column chromatography over silica gel using
11. additiona mixture of trichloromethane and methanol
12. customThe pure fractions were collected
13. customthe eluent was evaporated
14. customThe residue was crystallized from acetonitrile
15. filtrationThe product was filtered off
16. customdried