Methyl iodide → HCID 58368633, compound

HRID 1192711Notes

Reaction equation

HRID 1192711 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:13])[CH3:12])[C:8]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[H-].[Na+].[CH3:24]I>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[C:9]([C:11](=[O:13])[CH3:12])[C:8]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:24]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58368503HCID 58368503, compound

Product 1

HCID 58368633HCID 58368633, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-[4-chloro-7-(3,5-difluorophenyl)-1H-indazol-6-yl]ethanone (1.0 g, 3.3 mmol) in N,N-dimethylformamide (20 mL) was added sodium hydride (200 mg, 4.9 mmol). After being stirred at room temperature for 30 minutes, to the resulting mixture was added methyl iodide (0.30 mL, 4.9 mmol). The reaction was stirred at room temperature for another 30 minutes, then quenched with sat. ammonium chloride and extracted with Ethyl acetate. The combined organic layers were washed with water, brine and dried over sodium sulfate, then concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 30% ethyl acetate in hexane, to give the desired product (0.438 g, 42%). LCMS calculated for C16H12ClF2N2O (M+H)+: m/x=321.1; Found: 321.0. The other isomer, 1-[4-chloro-7-(3,5-difluorophenyl)-2-methyl-2H-indazol-6-yl]ethanone, was also isolated in a yield of 47%.

Workup

  1. stirringThe reaction was stirred at room temperature for another 30 minutes
  2. customquenched with sat. ammonium chloride
  3. extractionextracted with Ethyl acetate
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe residue was purified on silica gel
  8. washeluting with 0 to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c53b78d605c94437a96d2b8199744269
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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