Methyl iodide → 5-Bromo-4-methoxy-1-methyl-1H-indazole

HRID 1056982Notes

Reaction equation

HRID 1056982 reaction equation
[Br:1][C:2]1[C:3]([O:11][CH3:12])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[H-].[Na+].[CH3:15]I>CN(C)C=O.O.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([O:11][CH3:12])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:15])[N:6]=[CH:5]2

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 231345645-bromo-4-methoxy-1H-indazole

Product 1

HCID 847023345-Bromo-4-methoxy-1-methyl-1H-indazoleYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 5-bromo-4-methoxy-1H-indazole (0.125 g, 0.550 mmol) in N,N-dimethylformamide (2.20 mL) was treated with sodium hydride (0.0166 g, 0.659 mmol) at 20° C. and then stirred at 20° C. for 30 min. The resultant reaction mixture was treated with methyl iodide (0.0410 mL, 0.658 mmol) and stirred at 20° C. for 1 h. The reaction mixture was diluted with water and ethyl acetate. Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to give the crude product. Purification by flash column chromatography (100% hexanes to 100% EtOAc) gave the desired product (87 mg, 66%) as a white solid. LCMS calculated for C9H10BrN2O (M+H)+: m/z=241.0, 243.0. found: 240.9, 242.9.

Workup

  1. customThe resultant reaction mixture
  2. stirringstirred at 20° C. for 1 h
  3. customLayers were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customPurification by flash column chromatography (100% hexanes to 100% EtOAc)

Sources & evidence

ORD record
ord-4053e82448a041d39a3fc4895374e4b1
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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