4-Fluoroiodobenzene → 1-(4-Fluorophenyl)-1H-indazole-4-carboxylic acid 3-trifluoromethyl-benzylamide

HRID 2382929Notes

Reaction equation

HRID 2382929 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[CH2:6][NH:7][C:8]([C:10]1[C:11]2[CH:12]=[N:13][NH:14][C:15]=2[CH:16]=[CH:17][CH:18]=1)=[O:9].C(=O)([O-])[O-].[K+].[K+].[F:30][C:31]1[CH:36]=[CH:35][C:34](I)=[CH:33][CH:32]=1.CN[C@@H]1CCCC[C@H]1NC>O.C(OCC)(=O)C.[Cu]I>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[C:5]([CH:19]=[CH:20][CH:21]=1)[CH2:6][NH:7][C:8]([C:10]1[C:11]2[CH:12]=[N:13][N:14]([C:34]3[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=3)[C:15]=2[CH:16]=[CH:17][CH:18]=1)=[O:9]

Participants

8

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 581388541H-indazole-4-carboxylic acid 3-trifluoromethyl-benzylamide

Product 1

HCID 581388261-(4-Fluorophenyl)-1H-indazole-4-carboxylic acid 3-trifluoromethyl-benzylamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1H-indazole-4-carboxylic acid 3-trifluoromethyl-benzylamide (1.1 g, 3.4 mmol), copper(I) iodide (0.005 g, 0.02 mmol), potassium carbonate (0.04 g, 0.3 mmol) and 4-fluoroiodobenzene (0.04 g, 0.2 mmol) were charged in a sealed tube at room temperature. The tube was evacuated and back-filled with argon. The solids were dissolved in DMF (6 mL) and the resultant solution was treated with rac-trans-N,N′-dimethylcyclohexane-1,2-diamine (0.005 g, 0.04 mmol). The solution was stirred at 120° C. for 3 hours and cooled to room temperature. The solution was diluted with water (15 mL) and ethyl acetate (30 mL). The organic layer was separated, washed with brine and dried over sodium sulfate. The solvent was removed in vacuo. The crude residue was purified by silica gel chromatography eluting with a gradient of 10-40% ethyl acetate in hexanes to afford the title compound.

Workup

  1. additionwere charged in a sealed tube at room temperature
  2. customThe tube was evacuated
  3. additionback-filled with argon
  4. dissolutionThe solids were dissolved in DMF (6 mL)
  5. temperaturecooled to room temperature
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was removed in vacuo
  10. customThe crude residue was purified by silica gel chromatography
  11. washeluting with a gradient of 10-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-464755409ddc4817961167dc20c74f5f
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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