Potassium Iodide → 6-iodo-1H-indazole

HRID 2084048Notes

Reaction equation

HRID 2084048 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). The mixture was stirred for 30 minutes. Potassium iodide (13.5 g) was then added in small portions (gas evolution occurred) and the mixture 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 solids, and the solid was washed 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 removed in vacuo. Filtration chromatography on silica gel (35-60% ethyl acetate in hexane) gave a yellow solid which was triturated firstly with 50% ethyl acetate in hexane and then with ethyl acetate to yield the product (4.96 g).

Workup

  1. stirringthe mixture stirred for 1 h
  2. filtrationThe mixture was filtered
  3. customto remove solids
  4. washthe solid was washed 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 removed in vacuo
  12. filtrationFiltration chromatography on silica gel (35-60% ethyl acetate in hexane)
  13. customgave a yellow solid which
  14. customwas triturated firstly with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-602c58efde7744399b3f40beae3ee297
Source dataset
uspto-grants-2004_04
Patent number
US06716837B1

Reaction notes

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