4-Fluoroiodobenzene → 1-(4-Fluorophenyl)-1H-indazol-4-amine

HRID 551423Notes

Reaction equation

HRID 551423 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([NH2:10])[C:4]=2[CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.[F:27][C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1>CN(C=O)C.[Cu]I>[F:27][C:28]1[CH:33]=[CH:32][C:31]([N:1]2[C:9]3[CH:8]=[CH:7][CH:6]=[C:5]([NH2:10])[C:4]=3[CH:3]=[N:2]2)=[CH:30][CH:29]=1

Participants

7

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 11430Potassium Carbonate3×HCID 413085NoName_33272×HCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamine

Product 1

HCID 249380581-(4-Fluorophenyl)-1H-indazol-4-amineYield 369.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1H-indazol-4-amine (750 mg, 5.64 mmol), copper (I) iodide (247 mg, 1.3 mmol), potassium carbonate (1.56 g, 11.28 mmol), trans-N,N′-dimethyl-1,2-cyclohexanediamine (0.321 g, 2.26 mmol) and 4-fluoro-1-iodobenzene (0.78 ml, 6.77 mmol) in dry DMF (2 ml) was heated in a microwave reactor at 140° C. for 20 minutes (potassium carbonate was placed in the tube first and care was taken to avoid any particles of potassium carbonate being left on the side of the tube above the level of the liquid (in order to avoid any superheating). Three identical reactions plus two using 500 mg input of 1H-indazol-4-amine were then combined and partitioned between water and dichloromethane. The organic layer was evaporated and the residue purified by silica gel chromatography using the Flashmaster II (2×100 g cartridges) eluting with a 0 to 50% dichloromethane:ethyl acetate gradient over 60 minutes to give the title compound (4.73 g).

Workup

  1. waitleft on the side of the tube above the level of the liquid (in order
  2. custompartitioned between water and dichloromethane
  3. customThe organic layer was evaporated
  4. customthe residue purified by silica gel chromatography
  5. washeluting with a 0 to 50% dichloromethane

Sources & evidence

ORD record
ord-6f5180fad04340f9853c6ddfbbeafa53
Source dataset
uspto-grants-2011_05
Patent number
US07947727B2

Reaction notes

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