8-Hydroxyquinoline → 3-(2,5-Dimethylpyrrol-1-yl)-1-(3-fluorophenyl)-1H-pyrazole

HRID 83497

Reaction equation

HRID 83497 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:12]=[CH:11][NH:10][N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=CC=2O)C=CC=1.[F:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33](I)[CH:32]=1>CN1CCCC1=O.[Cu]=O.C1(C)C=CC=CC=1>[CH3:7][C:4]1[N:3]([C:8]2[CH:12]=[CH:11][N:10]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([F:30])[CH:32]=3)[N:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 707251-Fluoro-3-iodobenzeneHCID 178425430HCID 178425430, compound

Product 1

HCID 712877533-(2,5-Dimethylpyrrol-1-yl)-1-(3-fluorophenyl)-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 14829Copper oxideCatalystHCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-(2,5-dimethylpyrrol-1-yl)-1H-pyrazole (6.8 g) in N-methyl-2-pyrrolidone (68 ml) were sequentially added cesium carbonate (27.4 g), 8-quinolinol (1.2 g), copper oxide (I) (0.6 g) and 1-fluoro-3-iodobenzene (7.4 ml), and the mixture was stirred at 110° C. for 2 hours. This reaction mixture was cooled to room temperature, and toluene (80 ml) was added thereto, and then the mixture was filtered through Celite. After adding a 1M aqueous solution of sodium hydroxide (80 ml) to the filtrate, the mixture was extracted with toluene. The resulting organic layer was sequentially washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1) to give the titled compound (10.4 g).

Workup

  1. temperatureThis reaction mixture was cooled to room temperature
  2. filtrationthe mixture was filtered through Celite
  3. additionAfter adding a 1M aqueous solution of sodium hydroxide (80 ml) to the filtrate
  4. extractionthe mixture was extracted with toluene
  5. washThe resulting organic layer was sequentially washed with water
  6. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-be681fdb8c0f4f5e8dfdcac87443dbe7
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Linked notes

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