Methyl iodide → 5-bromo-3-iodo-1-methyl-1H-indazole

HRID 2263529Notes

Reaction equation

HRID 2263529 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[I:11].[CH3:12][O-].[Na+].CI>CO>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:12])[N:6]=[C:5]2[I:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 10942334Sodium MethoxideHCID 178419333HCID 178419333, compound

Product 1

HCID 231562265-bromo-3-iodo-1-methyl-1H-indazole

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 184.30 g of 5-bromo-3-iodo-1H-indazole [459133-66-5] in 2500 ml of methanol is admixed at 40° C. with 212 ml of a sodium methoxide solution (5.4M in methanol). 90 ml of methyl iodide are then added and the reaction mixture is heated to 65° C. After 30 minutes, the reaction mixture is cooled to room temperature, concentrated by evaporation to approx. 1000 ml, diluted with water and extracted with ethyl acetate (2×). The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a dark brown solid from the residue by means of flash chromatography (SiO2 60 F). Rf=0.68 (dichloromethane). Rt=4.94 (gradient I). As a by-product, the 5-bromo-3-iodo-2-methyl-2H-indazole regioisomer is also isolated as a red-orange solid. Rf=0.52 (dichloromethane). Rt=4.58 (gradient I).

Workup

  1. temperaturethe reaction mixture is cooled to room temperature
  2. concentrationconcentrated by evaporation to approx. 1000 ml
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate (2×)
  5. dry with materialThe combined organic phases are dried over sodium sulphate
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-04807f9990aa4b55b884e7c231c1f535
Source dataset
uspto-grants-2010_12
Patent number
US07851634B2

Reaction notes

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