Methyl iodide → 4-Bromo-5-isopropyl-1-methylindazole

HRID 857943Notes

Reaction equation

HRID 857943 reaction equation
[Br:1][C:2]1[C:10]([CH:11]([CH3:13])[CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[H-].[Na+].I[CH3:17]>CN(C=O)C>[Br:1][C:2]1[C:10]([CH:11]([CH3:13])[CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:17]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 225669164-Bromo-5-isopropyl-1H-indazole

Product 1

HCID 225669734-Bromo-5-isopropyl-1-methylindazoleYield 65.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-bromo-5-isopropylindazole (27) (488 mg, 2.04 mmol) in 5 nml of anhydrous DMF is added to a suspension of sodium hydride (122 mg, 60% in mineral oil, 3.06 mmol, 1.5 eq.) in 5 ml of DMF under nitrogen at 0° C. The resulting mixture is stirred at 0° C. for 30 minutes, then warmed to room temperature. After stirring at room temperature for an additional 2 hours, the reaction mixture is cooled to 0° C., and iodomethane (318 mg, 2.24 mmol, 1.1 eq.) is added dropwise, the mixture is stirred at 0° C. for 2 hours, then warmed to room temperature, and stirred overnight. The reaction mixture is poured into 30 ml of ice-water, extracted with ethyl acetate (30 ml×3), washed with water and brine, and dried over anhydrous sodium sulfate. The solvent is evaporated and the product is purified via flash chromatography to give 340 mg of 4-bromo-5-isopropyl-1-methylindazole 1H NMR (400 MHz, CDCl3) 7.95 (1H, s), 7.31 (2H, S), 4.05 (3H, S), 3.55 (1H, m), 1.27 (6H, d, J=6.8 Hz). MS (+VE) m/z 253(M+). 165 mg of 4-bromo-5-isopropyl-2-methylindazole (28). 1H NMR (400 MHz, CDCl3) δ 7.82 (1H, s), 7.59 (1H, d, J=9.2 Hz), 7.21 (1H, d, J=8.8 Hz), 4.16 (3H, s), 3.50 (1H, m), 1.21 (6H, d, J=6.8 Hz). MS (+VE) m/z 253(M+).

Workup

  1. temperaturewarmed to room temperature
  2. stirringAfter stirring at room temperature for an additional 2 hours
  3. temperaturethe reaction mixture is cooled to 0° C.
  4. stirringthe mixture is stirred at 0° C. for 2 hours
  5. temperaturewarmed to room temperature
  6. stirringstirred overnight
  7. extractionextracted with ethyl acetate (30 ml×3)
  8. washwashed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent is evaporated
  11. customthe product is purified via flash chromatography

Sources & evidence

ORD record
ord-e279da97780e474883de344fccf6f3fa
Source dataset
uspto-grants-2006_12
Patent number
US07148225B2

Reaction notes

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