Hydrochloric Acid → 5-Bromo-1-methyl-1H-indazole

HRID 909152Notes

Reaction equation

HRID 909152 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[H-].[Na+].I[CH3:14].Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:14])[N:6]=[CH:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 7619295-bromo-1H-indazole

Product 1

HCID 225587255-Bromo-1-methyl-1H-indazoleYield 76.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

5-Bromo-1H-indazole (1r) (10 g, 51 mmol) in THF was added slowly to a cold solution of NaH (2.2 g, 60% wt in oil, 56 mmol) in THF under nitrogen. After 15 minutes, iodomethane (10.8 g, 76 mmol) was added to the dark solution at 0° C. After 2 hours, the mixture was poured into 1N HCl (30 mL) and extracted with EtOAc (2×50 mL), and the combined extracts were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. Column chromatography (silica gel): hexane:EtOAc (10-40%) resulted in 8.2 g of final product (2r). 1H NMR (400 MHz, CDCl3) δ 7.9 (s, 1H), 7.84 (s, 1H), 7.43 (d, J=8.8 Hz, 1H), 7.24 (d, J=8.8 Hz, 1H), 4.04 (s, 3H); MS (ESI) m/z 213 (M+H)+.

Workup

  1. waitAfter 2 hours
  2. extractionextracted with EtOAc (2×50 mL)
  3. washthe combined extracts were washed with brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d4b8934f3b87497db07099d5f8990d62
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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