Réaction #2188

Équation de réaction

(±)-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

Rendement 39.4%

Solvants

hydrobromic acid

water

Conditions de réaction

Traitement

1. 1
   Températurerefluxed overnight
2. 2
   AutreThe solvent was evaporated
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2
4. 4
   Extractionextracted with CH2 Cl2
5. 5
   LavageThe organic layer was washed with water
6. 6
   Autredried
7. 7
   Filtrationfiltered
8. 8
   Autreevaporated
9. 9
   AutreA 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
    AutreThe pure fractions were collected
11. 11
    Autreevaporated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in 2-propanol
13. 13
    Autrecrystallized into the hydrochloric acid salt (1:1) in 2-propanol
14. 14
    FiltrationThe precipitate was filtered off
15. 15
    Lavagewashed with 2-propanol
16. 16
    Autredried 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
    Autresubsequently crystallized
21. 21
    FiltrationThe precipitate was filtered off
22. 22
    Autredried

Mode opératoire

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).

Source