反应详情

A mixture of (±)-ethyl 4-[5-[2-[1-(4-chlorobenzoyl)propyl]-2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl]-2-pyridinyl]-1-piperazinecarboxylate (24 g) in hydrobromic acid, 48% solution in water (250 ml) was stirred and refluxed overnight. The solvent was evaporated and the residue was dissolved in CH2Cl2, neutralized with NH4OH/H2O and extracted with CH2 Cl2. The organic layer was washed with water, dried, filtered and evaporated. A sample (3.5 g) of the residue (total 18 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 99/1). The pure fractions were collected and evaporated. The residue was dissolved in 2-propanol and crystallized into the hydrochloric acid salt (1:1) in 2-propanol. The precipitate was filtered off, washed with 2-propanol and dried at 150° C. The product was dissolved in 2-propanol. Pyridine was added dropwise until all the product was dissolved and subsequently crystallized. The precipitate was filtered off and dried, yielding 1.7 g (±)-2-[1-(4-chlorobenzoyl)propyl]-2,4-dihydro-4-[6-(1-piperazinyl)-3-pyridinyl]-3H-1,2,4-triazol-3-one monohydrochloride (39.4%); mp. 209.8° C. (interm. 1).

1. temperaturerefluxed overnight
2. customThe solvent was evaporated
3. dissolutionthe residue was dissolved in CH2Cl2
4. extractionextracted with CH2 Cl2
5. washThe organic layer was washed with water
6. customdried
7. filtrationfiltered
8. customevaporated
9. customA sample (3.5 g) of the residue (total 18 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 99/1)
10. customThe pure fractions were collected
11. customevaporated
12. dissolutionThe residue was dissolved in 2-propanol
13. customcrystallized into the hydrochloric acid salt (1:1) in 2-propanol
14. filtrationThe precipitate was filtered off
15. washwashed with 2-propanol
16. customdried at 150° C
17. dissolutionThe product was dissolved in 2-propanol
18. additionPyridine was added dropwise until all the product
19. dissolutionwas dissolved
20. customsubsequently crystallized
21. filtrationThe precipitate was filtered off
22. customdried