Methyl iodide → HCID 71280384, compound

HRID 246226Notes

Reaction equation

HRID 246226 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:12])=[C:8]([F:11])[CH:9]=2)[NH:4][N:3]=1.[C:13](=O)([O-])[O-].[K+].[K+].IC.CC(=O)OCC>CN1CCCC1>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:12])=[C:8]([F:11])[CH:9]=2)[N:4]([CH3:13])[N:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 178505408HCID 178505408, compound

Product 1

HCID 71280384HCID 71280384, compound

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Procedure

To a light brown suspension of 3-bromo-5,6-difluoro-1H-indazole (1.0 g, 4.29 mmol) and potassium carbonate (4.15 g, 30.0 mmol) in N-methylpyrrolidine (20 mL) was added iodomethane (0.81 mL, 12.9 mmol) at room temperature. The resulting dark brown solution was stirred for 15 h at room temperature under nitrogen atmosphere by which time the TLC (2:1, Hex:EA, Rf=0.6, major and 0.4, minor) indicated the presence of the desired compound. The reaction was diluted with water (˜100 mL), the organic compound was extracted with ethyl acetate (3×50 mL) and the combined extracts were washed with brine solution. After drying over MgSO4, the filtrate was concentrated to obtain the crude light brown solid which was purified by chromatography using an ISCO (80 g) column eluting with hexanes (1 min), 0-15% EA in hexanes (2 min), 15-40% EA in hexanes (15 min) to obtain 746 mg (70%) of 3-bromo-5,6-difluoro-1-methyl-1H-indazole as a white solid and 186 mg (18%) of 3-bromo-5,6-difluoro-2-methyl-2H-indazole as a light yellow solid.

Sources & evidence

ORD record
ord-cfc1c4680d794b9f94ac7282f607ae4d
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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