Sulfuric Acid → 5-Iodo-1-methyl-1H-indazole

HRID 1253822Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](N)=[CH:8][CH:9]=2)[CH:4]=[N:3]1.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:21].[Na+].[OH-].[Na+]>O>[I:21][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:2]([CH3:1])[N:3]=[CH:4]2

Participants

Conditions

Temperature: 0 °C

Procedure

To 1-Methyl-1H-indazol-5-amine (500 mg, 3.40 mmol) in a mixture of concentrated sulfuric acid (1.3 ml) and water (5.5 ml) cooled down to 0° C., was added dropwise a solution of sodium nitrite (258 mg, 3.74 mmol) in water (0.5 ml). The reaction mixture was stirred at 0° C. for 10 minutes then added dropwise to a solution of sodium iodide (1.5 g) in water (4.5 ml) cooled to 0° C. After complete addition, the reaction mixture was heated to 90° C. for an additional 20 minutes. The resultant mixture was basified with a diluted solution of sodium hydroxide and extracted with ethylacetate. The organic phase was washed further with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography eluting with 20% EtOAc in petroleum ether to afford the title compound (475 mg, 54% yield). 1H NMR (DMSO D6, 400 MHz) 4.03 (3H, s), 7.52 (1H, d), 7.63 (1H, dd), 7.99 (1H, s), 8.17 (1H, s).

Workup

temperaturecooled to 0° C
additionAfter complete addition
temperaturethe reaction mixture was heated to 90° C. for an additional 20 minutes
extractionextracted with ethylacetate
washThe organic phase was washed further with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe residue was purified on silica gel by flash column chromatography
washeluting with 20% EtOAc in petroleum ether

Sources & evidence

ORD record: ord-74f8b9e86c9e49a7aa7e26adf58438ec
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455507B2

Reaction notes

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