반응 #2188

반응 방정식

(±)-ethyl 4-[5-[2-[1-(4-chlorobenzoyl)propyl]-2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl]-2-pyridinyl]-1-piperazinecarboxylate

→

(±)-2-[1-(4-chlorobenzoyl)propyl]-2,4-dihydro-4-[6-(1-piperazinyl)-3-pyridinyl]-3H-1,2,4-triazol-3-one monohydrochloride

수율 39.4%

용매

hydrobromic acid

water

반응 조건

후처리

1. 1
   온도refluxed overnight
2. 2
   기타The solvent was evaporated
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2
4. 4
   추출extracted with CH2 Cl2
5. 5
   세척The organic layer was washed with water
6. 6
   기타dried
7. 7
   여과filtered
8. 8
   기타evaporated
9. 9
   기타A 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. 10
    기타The pure fractions were collected
11. 11
    기타evaporated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in 2-propanol
13. 13
    기타crystallized into the hydrochloric acid salt (1:1) in 2-propanol
14. 14
    여과The precipitate was filtered off
15. 15
    세척washed with 2-propanol
16. 16
    기타dried at 150° C
17. 17
    workup.DISSOLUTIONThe product was dissolved in 2-propanol
18. 18
    workup.ADDITIONPyridine was added dropwise until all the product
19. 19
    workup.DISSOLUTIONwas dissolved
20. 20
    기타subsequently crystallized
21. 21
    여과The precipitate was filtered off
22. 22
    기타dried

실험 절차

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).

출처