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 525222Notes

Reaction equation

HRID 525222 reaction equation
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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 11430Potassium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-0fed73267be7407ca31003d31e6dbc3d
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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