8-Hydroxyquinoline → 1-(4-Chlorophenyl)-3-(2,5-dimethylpyrrol-1-yl)-1H-pyrazole

HRID 83533

Reaction equation

HRID 83533 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.[Cl:30][C:31]1[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=1>CN1CCCC1=O.[Cu-]=O.C1(C)C=CC=CC=1>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([N:10]2[CH:11]=[CH:12][C:8]([N:3]3[C:2]([CH3:1])=[CH:6][CH:5]=[C:4]3[CH3:7])=[N:9]2)=[CH:33][CH:32]=1

Participants

8

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 125101-Chloro-4-iodobenzeneHCID 178425430HCID 178425430, compound

Product 1

HCID 866803671-(4-Chlorophenyl)-3-(2,5-dimethylpyrrol-1-yl)-1H-pyrazoleYield 96.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

Under argon atmosphere, to a solution of 3-(2,5-dimethylpyrrol-1-yl)-1H-pyrazole (3.06 g) prepared according to the same procedures as Preparation 4 in N-methylpyrrolidone (31 ml) were sequentially added cesium carbonate (12.37 g), 8-quinolinol (0.55 g), copper (I) oxide (0.27 g) and 1-chloro-4-iodobenzene (6.79 g) at room temperature, the mixture was stirred at 110° C. for 2 hours. This reaction mixture was cooled to room temperature, and then toluene (30 ml) was added thereto, the mixture was filtered through Celite, and further subjected to elution with toluene. The filtrate was sequentially washed with a 1N aqueous solution of sodium hydroxide, water, 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 9/1) to give the titled compound (4.98 g).

Workup

  1. customat room temperature
  2. temperatureThis reaction mixture was cooled to room temperature
  3. filtrationthe mixture was filtered through Celite
  4. washfurther subjected to elution with toluene
  5. washThe filtrate was sequentially washed with a 1N aqueous solution of sodium hydroxide, 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=1/0 to 9/1)

Sources & evidence

ORD record
ord-7b4191a76f0643c9b6f8e47b5d240bc2
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Linked notes

Loading…