Methyl iodide → 5,6-dichloro-3-iodo-1-methyl-1H-indazole
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][N:6]=[C:5]2[I:12].[CH3:13]C([O-])(C)C.[K+].IC>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[N:7]([CH3:13])[N:6]=[C:5]2[I:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 5,6-dichloro-3-iodo-1H-indazole (820 mg, 2.62 mmol) in THF (8 ml) at 0° C. was added KOt-Bu (412 mg, 3.67 mmol). The reaction mixture was stirred at 0° C. for 30 min then added iodomethane (0.23 ml, 3.67 mmol). Stirred at 0° C. for 30 min then warmed to room temperature and stirred for 1.5 hr. The reaction was quenched with water and extracted with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The crude residue was absorbed on silica gel and purified by chromatography with 20% to 30% EtOAc/hexanes to afford 585 mg (68%) of 5,6-dichloro-3-iodo-1-methyl-1H-indazole as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 7.61 (s, 1H), 7.56 (s, 1H), 4.09 (s, 3H). The minor 5,6-dichloro-3-iodo-2-methyl-1H-indazole regioisomer was also observed but not isolated.
Workup
- stirringStirred at 0° C. for 30 min
- temperaturethen warmed to room temperature
- stirringstirred for 1.5 hr
- customThe reaction was quenched with water
- extractionextracted with EtOAc (2×)
- dry with materialThe combined organics were dried over MgSO4
- concentrationconcentrated
- customThe crude residue was absorbed on silica gel
- custompurified by chromatography with 20% to 30% EtOAc/hexanes
Sources & evidence
- ORD record
- ord-b1241fa3c77f4de9b5392de933503469
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658646B2
Reaction notes
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