Methyl iodide → 7-fluoro-6-(2-fluoro-phenylamino)-1,3-dimethyl-1H-indazole-5-carboxylic acid methyl ester

HRID 558230Notes

Reaction equation

HRID 558230 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[C:12]([F:22])[C:11]2[C:7](=[C:8]([CH3:23])[NH:9][N:10]=2)[CH:6]=1)=[O:4].[C:24](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])=[C:12]([F:22])[C:11]2[C:7](=[C:8]([CH3:23])[N:9]([CH3:24])[N:10]=2)[CH:6]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[C:12]([F:22])[C:13]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[F:21])[N:10]([CH3:24])[N:9]=[C:8]2[CH3:23])=[O:4]

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 595194097-fluoro-6-(2-fluoro-phenylamino)-3-methyl-2H-indazole-5-carboxylic acid methyl ester

Product 2

HCID 595194847-fluoro-6-(2-fluoro-phenylamino)-2,3-dimethyl-2H-indazole-5-carboxylic acid methyl esterYield 26%HCID 669993577-fluoro-6-(2-fluoro-phenylamino)-1,3-dimethyl-1H-indazole-5-carboxylic acid methyl esterYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-fluoro-6-(2-fluoro-phenylamino)-3-methyl-2H-indazole-5-carboxylic acid methyl ester (146 mg, 0.46 mmol) in DMF (5 ml) were added potassium carbonate (95 mg, 069 mmol) and iodomethane (0.034 mL, 0.55 mmol). The reaction was stirred at room temp overnight, diluted with EtOAc and washed with H2O. The organic fraction was dried over MgSO4 and concentrated under reduced pressure. Silica gel chromatography (EtOAc:Hexanes=75:25) yielded 40 mg (26%) of the title compound and 81 mg (53%) of 7-fluoro-6-(2-fluoro-phenylamino)-1,3-dimethyl-1H-indazole-5-carboxylic acid methyl ester.

Workup

  1. washwashed with H2O
  2. dry with materialThe organic fraction was dried over MgSO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-482bacc4852b41acb27724f0611ae713
Source dataset
uspto-grants-2011_11
Patent number
US08063049B2

Reaction notes

Loading…