(+/-)-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

HRID 1898869

반응식

HRID 1898869 반응식
[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([C:6]([CH:8]([N:11]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:28][CH2:27][N:26](C(OCC)=O)[CH2:25][CH2:24]4)=[N:21][CH:22]=3)[CH:13]=[N:12]2)[CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1>Br.O>[ClH:1].[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([C:6]([CH:8]([N:11]2[C:15](=[O:16])[N:14]([C:17]3[CH:22]=[N:21][C:20]([N:23]4[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]4)=[CH:19][CH:18]=3)[CH:13]=[N:12]2)[CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1

참가 물질

4

반응물 1

HCID 53958409(+/-)-ethyl 4-[5-[2-[1-(4-chlorobenzoyl)propyl]-2,3-dihydro-3-oxo-4H-1,2,4-triazol-4-yl]-2-pyridinyl]-1-piperazinecarboxylate

생성물 1

HCID 18972843(+/-)-2-[1-(4-chlorobenzoyl) propyl]2,4-dihydro-4-[6-(1-piperazinyl)-3-pyridinyl]-3H-1,2,4-triazol-3-one monohydrochloride수율 39.4%

시약·촉매·용매 2

HCID 260Hydrogen Bromide용매HCID 962Water용매

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 CH2Cl2. 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). b) A mixture of benzenesulfonyl chloride (0.044 g) and intermediate 1(0.1 g) in CH2Cl2 (10 ml) and N,N-diethylethanamine (1 ml) was stirred at room temperature overnight. The mixture was purified by HPLC over silica gel (eluent: CH2Cl2 100 to CH2Cl2 /CH3OH 90/10 over a 20 minutes period and 120ml/min.). The desired fraction was collected and evaporated, yielding a solution of 0.119 g (85%) in DMSO (10.5 ml) of (±)-1-[5-[2-[1-(4-chlorobenzoyl)propyl]-2,3-dihydro-3-oxo-4H-1,2,4-triazol-4yl]-2-Pyridinyl]-4-(phenylsulfonyl)piperazine (comp. 1). In a similar manner were prepared:

후처리

  1. temperaturerefluxed overnight
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in CH2Cl2
  4. extractionextracted with CH2Cl2
  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

출처 및 근거

ORD 기록
ord-94579f9541b24d3994b0f513c1fd500b
출처 데이터셋
uspto-grants-1996_11
특허 번호
US05571811

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