Methyl iodide → 6-(tert-Butyl)-3-iodo-1-methyl-1H-indazole

HRID 246026Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 6-tert-butyl-3-iodo-1H-indazole (820 mg, 2.73 mmol) in THF (8 ml) at 0° C. was added KOt-Bu (429 mg, 3.82 mmol). The reaction mixture was stirred at 0° C. for 30 min then added iodomethane (0.24 ml, 3.82 mmol). Stirred at 0° C. for 30 min then warmed to room temperature and stirred for 1.5 h. The reaction was quenched with water and extracted with EtOAc (2×). The combined organics were washed with brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 10% to 50% EtOAc/heptane to afford 592 mg (69%) of 6-tert-butyl-3-iodo-1-methyl-1H-indazole as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.37-7.43 (m, 1H), 7.31 (d, J=9.8 Hz, 2H), 4.10 (s, 3H), 1.41 (s, 9H). The minor 6-tert-butyl-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 h
customThe reaction was quenched with water
extractionextracted with EtOAc (2×)
washThe combined organics were washed with brine
dry with materialthen dried over MgSO4
concentrationconcentrated
customThe crude residue was purified by silica gel chromatography with 10% to 50% EtOAc/heptane

Sources & evidence

ORD record: ord-8ab12789955740a8a1281fdbc9467c7b
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

Loading…