Ethanol → 4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-[(1-propanoyl-3-azetidinyl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405406노트

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HRID 2405406 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][CH:14]3[CH2:17][N:16]([C:18](=[O:21])[CH2:19][CH3:20])[CH2:15]3)=[N:11][N:10](C(=O)CC)[C:9]2=[O:26])=[C:4]([F:27])[CH:3]=1.[N:28]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35](B(O)O)[CH:36]=2)[CH:31]=[CH:30][CH:29]=1.C(O)C>O1CCOCC1.C(=O)([O-])[O-].[K+].[K+].ClCCl>[F:27][C:4]1[CH:3]=[C:2]([C:35]2[CH:36]=[C:37]3[C:32]([CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:33][CH:34]=2)[CH:7]=[CH:6][C:5]=1[N:8]1[C:12]([CH2:13][CH:14]2[CH2:15][N:16]([C:18](=[O:21])[CH2:19][CH3:20])[CH2:17]2)=[N:11][NH:10][C:9]1=[O:26]

참가 물질

7

반응물 3

HCID 702EthanolHCID 21886457Quinoline-7-boronic acidHCID 673760194-(4-bromo-2-fluorophenyl)-2-propanoyl-5-[(1-propanoyl-3-azetidinyl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

생성물 1

HCID 673554144-[2-fluoro-4-(7-quinolinyl)phenyl]-5-[(1-propanoyl-3-azetidinyl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 11430Potassium Carbonate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

In a microwave vial purged with nitrogen, a mixture of 4-(4-bromo-2-fluorophenyl)-2-propanoyl-5-[(1-propanoyl-3-azetidinyl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.37 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.02 mmol) and 7-quinoline boronic acid (0.39 mmol) in 1,4-dioxane (2 mL) and 2M aq potassium carbonate (2 mL) was stirred at 100° C. in an oil bath for 1 h. The reaction was cooled to room temperature and the layers were separated. The aqueous layer was acidified to pH˜5.5 using 1N HCl solution and extracted with ethyl acetate (50 mL). The organic layers were combined, dried over magnesium sulphate, and concentrated in vacuo to give a tan solid. Trituration in dichloromethane followed by treatment with hot ethanol (5 mL), which was allowed to cool to room temperature, and then filtration afforded the desired product as a white solid, 93% pure. Subsequent purification of the filtrate and white solid by reverse phase HPLC (20-60% acetonitrile/water with 0.1% NH4OH) provided the title compound as a white solid (119 mg, 74%). MS(ES)+ m/e 432.1 [M+H]+.

후처리

  1. customIn a microwave vial purged with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. customthe layers were separated
  4. extractionextracted with ethyl acetate (50 mL)
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. customto give a tan solid
  8. temperatureto cool to room temperature
  9. filtrationfiltration

출처 및 근거

ORD 기록
ord-688cc0fa82cb459a9b026665814a7475
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08802864B2

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