Potassium Iodide → 6-iodo-1H-indazole

HRID 988113Notes

Reaction equation

HRID 988113 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[N:11][NH:12]2)=[CH:8][CH:7]=1.[I-:15].[K+].S(=O)(O)[O-].[Na+].[OH-].[Na+]>O.CN(C=O)C.Cl>[I:15][C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[N:11][NH:12]2)=[CH:8][CH:7]=1

Participants

9

Reactant 5

HCID 4875Potassium IodideHCID 14798Sodium HydroxideHCID 814231H-Indazol-6-amineHCID 23665763Sodium BisulfiteHCID 23668193Sodium Nitrite

Product 1

HCID 129912416-iodo-1H-indazoleYield 26.9%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium nitrite (5.87 g, 85 mmol) in water (20 mL) was added dropwise to an ice-cooled solution of 6-aminoindazole (10 g, 75.6 mmol) in DMF (80 mL) and hydrochloric acid (6M, 40 mL) and the mixture was stirred for 30 minutes. Potassium iodide (13.5 g) was then added in small portions (gas evolution occurred) and the mixture was stirred for 1 h before warming to room temperature for 16 h. The reaction was neutralized with aqueous sodium bisulfite followed by aqueous sodium hydroxide. The mixture was filtered to remove solid, and the solid was washed first with water to remove impurities, and then with ethyl acetate and THF to collect the product. The organic washes were evaporated and recombined with the aqueous layer for extraction with ethyl acetate (3×250 mL). The organic layer was washed sequentially with water and brine, dried over sodium sulfate, and the solvent was removed in vacuo. Filtration chromatography on silica gel (35-60% ethyl acetate in hexane) yield a yellow solid, which was then triturated with 50% ethyl acetate in hexane and finally ethyl acetate to yield the product (4.96 g).

Workup

  1. stirringthe mixture was stirred for 1 h
  2. filtrationThe mixture was filtered
  3. customto remove solid
  4. washthe solid was washed first with water
  5. customto remove impurities
  6. customwith ethyl acetate and THF to collect the product
  7. customThe organic washes were evaporated
  8. extractionrecombined with the aqueous layer for extraction with ethyl acetate (3×250 mL)
  9. washThe organic layer was washed sequentially with water and brine
  10. dry with materialdried over sodium sulfate
  11. customthe solvent was removed in vacuo
  12. filtrationFiltration chromatography on silica gel (35-60% ethyl acetate in hexane)
  13. customyield a yellow solid, which
  14. customwas then triturated with 50% ethyl acetate in hexane and finally ethyl acetate

Sources & evidence

ORD record
ord-7f1254c3908245bf83a83b7cca82c461
Source dataset
uspto-grants-2003_10
Patent number
US06635639B2

Reaction notes

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