Methyl iodide → 3-Iodo-1-methyl-6-(methylsulfonyl)-1H-indazole

HRID 246324Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

In a round-bottomed flask, 3-iodo-6-methylsulfonyl-1H-indazole (396 mg, 1.23 mmol) was dissolved in THF (4.4 ml). The orange solution was cooled to 0° C. and potassium tert-butoxide (200 mg, 1.78 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then iodomethane (0.11 ml, 1.76 mmol) was added dropwise. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 4 h then quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient: 0-30% EtOAc) to give 251 mg (61%) of 3-iodo-6-methanesulfonyl-1-methyl-1H-indazole as an off-white solid. The minor regioisomer 3-iodo-6-methanesulfonyl-2-methyl-2H-indazole was also observed, but not isolated.

Workup

additionAfter the addition
customthe ice bath was removed
stirringthe reaction mixture was stirred at room temperature for 4 h
customthen quenched with water
extractionextracted with EtOAc (2×)
washThe combined organic layers were washed with water and brine
dry with materialthen dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was absorbed on silica gel
customchromatographed with EtOAc/hexanes (gradient: 0-30% EtOAc)

Sources & evidence

ORD record: ord-9cddb34b0a254596b9a0089c0a49245c
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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