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

HRID 83538

Reaction equation

HRID 83538 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.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1I.N1C2C(=CC=CC=2O)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[F:13])[N:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 676731-Fluoro-2-iodobenzeneHCID 178425430HCID 178425430, compound

Product 1

HCID 866803713-(2,5-Dimethylpyrrol-1-yl)-1-(2-fluorophenyl)-1H-pyrazole

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-(2,5-dimethylpyrrol-1-yl)-1H-pyrazole (1.00 g) prepared according to the same procedures as Preparation 4 in N-methylpyrrolidone (10 ml) were sequentially added 1-fluoro-2-iodobenzene (1.08 ml), copper (I) oxide (89 mg), 8-quinolinol (180 mg) and cesium carbonate (4.04 g) at room temperature, and the mixture was stirred at 110° C. for 3 hours. This reaction mixture was cooled to room temperature, and then toluene was added thereto, and the mixture was filtered through Celite. The filtrate was sequentially washed with a 2N aqueous solution of sodium hydroxide, water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 10/1) to give the titled compound (1.19 g).

Workup

  1. customat room temperature
  2. temperatureThis reaction mixture was cooled to room temperature
  3. filtrationthe mixture was filtered through Celite
  4. washThe filtrate was sequentially washed with a 2N aqueous solution of sodium hydroxide, water
  5. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 10/1)

Sources & evidence

ORD record
ord-a21e600cd7d34c8eafc6b8fb94ebf901
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Linked notes

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