Methyl iodide → 6-Bromo-1-methyl-1H-indazole

HRID 2112563

Reaction equation

HRID 2112563 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:13]I>C1COCC1>[CH3:13][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Br:1])[CH:10]=2)[CH:6]=[N:7]1.[CH3:13][N:7]1[CH:6]=[C:5]2[C:9]([CH:10]=[C:2]([Br:1])[CH:3]=[CH:4]2)=[N:8]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178424716-Bromo-1H-indazole

Product 2

HCID 225586246-bromo-2-methyl-2H-indazoleYield 43%HCID 225586756-Bromo-1-methyl-1H-indazoleYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 6-bromoindazole (402A) (5.0 g, 25.4 mmol) in THF (50 mL) was added sodium hydride (95%, 672 mg, 26.6 mmol) with ice bath cooling. The mixture was stirred for 30 minutes. Methyl iodide (6.36 mL, 102 mmol) was added at room temperature. The reaction mixture was quenched with ammonium chloride solution and the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over sodium sulfate and concentrated. Purification by column chromatography (SiO2, ethyl acetate/hexane gradient) afforded 1-methyl-6-bromoindazole (402B) (2.71 g, 51%) as a yellow oil and 2-methyl-6-bromoindazole (402C) (2.28 g, 43%) as a yellow crystalline solid.

Workup

  1. temperaturecooling
  2. customThe reaction mixture was quenched with ammonium chloride solution
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by column chromatography (SiO2, ethyl acetate/hexane gradient)

Sources & evidence

ORD record
ord-588c98c774694becb0aeae6eb415fe31
Source dataset
uspto-grants-2009_04
Patent number
US07524842B2

Linked notes

Loading…