反応 #2188

反応方程式

(±)-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

収率 39.4%

溶媒

hydrobromic acid

water

反応条件

後処理

1. 1
   温度refluxed overnight
2. 2
   その他The solvent was evaporated
3. 3
   workup.DISSOLUTIONthe residue was dissolved in CH2Cl2
4. 4
   抽出extracted with CH2 Cl2
5. 5
   洗浄The organic layer was washed with water
6. 6
   その他dried
7. 7
   ろ過filtered
8. 8
   その他evaporated
9. 9
   その他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)
10. 10
    その他The pure fractions were collected
11. 11
    その他evaporated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in 2-propanol
13. 13
    その他crystallized into the hydrochloric acid salt (1:1) in 2-propanol
14. 14
    ろ過The precipitate was filtered off
15. 15
    洗浄washed with 2-propanol
16. 16
    その他dried 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
    その他subsequently crystallized
21. 21
    ろ過The precipitate was filtered off
22. 22
    その他dried

実験手順

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).

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