Reaktion #2188

Reaktionsgleichung

(±)-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

Ausbeute 39.4%

Lösungsmittel

hydrobromic acid

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturrefluxed overnight
2. 2
   SonstigeThe solvent was evaporated
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2
4. 4
   Extraktionextracted with CH2 Cl2
5. 5
   WaschenThe organic layer was washed with water
6. 6
   Sonstigedried
7. 7
   Filtrationfiltered
8. 8
   Sonstigeevaporated
9. 9
   SonstigeA 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
    SonstigeThe pure fractions were collected
11. 11
    Sonstigeevaporated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in 2-propanol
13. 13
    Sonstigecrystallized into the hydrochloric acid salt (1:1) in 2-propanol
14. 14
    FiltrationThe precipitate was filtered off
15. 15
    Waschenwashed with 2-propanol
16. 16
    Sonstigedried 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
    Sonstigesubsequently crystallized
21. 21
    FiltrationThe precipitate was filtered off
22. 22
    Sonstigedried

Vorschrift

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).

Quelle