Methyl iodide → 3-iodo-1-methyl-5-(methylsulfonyl)-1H-indazole

HRID 246772Notes

Reaction equation

HRID 246772 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:9]=2)[NH:4][N:3]=1.[CH3:15]C([O-])(C)C.[K+].IC>C1COCC1>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([S:11]([CH3:14])(=[O:12])=[O:13])[CH:9]=2)[N:4]([CH3:15])[N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23665647Potassium tert-butoxideHCID 178504659HCID 178504659, compound

Product 1

HCID 712795273-iodo-1-methyl-5-(methylsulfonyl)-1H-indazoleYield 50.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-iodo-5-(methylsulfonyl)-1H-indazole (400 mg, 1.24 mmol) in THF (15 mL) was added t-BuOK (208 mg, 1.86 mmol) slowly at 0° C., mixture stirred for 30 minutes, then iodomethane (262 mg, 1.86 mmol) was added at 0° C., then warmed to room temperature and stirred for 2 hours. Reaction quenched with water (40 mL) and product extracted with EtOAc (3×30 mL), organics combined dried with sodium sulfate, filtered and concentrated under reduced pressure to afford a solid which was purified by column chromatography (silica gel, 200-300 mesh, eluting with dichloromethane/methanol=10:1) to give 3-iodo-1-methyl-5-(methylsulfonyl)-1H-indazole (210 mg, 50.6%) as a white solid. LCMS: (M+H)+=337; 1H NMR (300 MHz, DMSO): δ 7.97-7.94 (m, 3H), 4.13 (s, 3H), 3.26 (s, 3H).

Workup

  1. stirringstirred for 2 hours
  2. customReaction
  3. customquenched with water (40 mL) and product
  4. extractionextracted with EtOAc (3×30 mL)
  5. dry with materialorganics combined dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto afford a solid which
  9. customwas purified by column chromatography (silica gel, 200-300 mesh, eluting with dichloromethane/methanol=10:1)

Sources & evidence

ORD record
ord-d6e07b073fcf4d89bcd291b2f4b111ba
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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