Hydroxyamine hydrochloride → 5-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

HRID 2088966Notes

Reaction equation

HRID 2088966 reaction equation
Cl.[NH2:2]O.[Br:4][C:5]1[CH:6]=[C:7]2[C:13]([CH:14]=O)=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1.C(=O)(O)[O-].[Na+]>CO>[Br:4][C:5]1[CH:6]=[C:7]2[C:13]([C:14]#[N:2])=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1

Participants

5

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 247296055-bromo-1H-pyrrolo(2,3-b)pyridine-3-carbaldehyde

Product 1

HCID 280587935-Bromo-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Hydroxylamine hydrochloride (46 mg) was added to a suspension of 5-bromo-1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde obtained by the method of described in WO 2004/101565 (150 mg) in methanol (1.0 ml) under nitrogen atmosphere, and the mixture was stirred at room temperature for one hour. After azeotropic distillation with toluene, thionyl chloride (118 μl) was added to a suspension of the residue in toluene (2 ml), and the mixture was stirred at 80° C. for 16 hours and at 100° C. for 8 hours. After leaving to cool to room temperature, saturated aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developed with methanol-chloroform) to give the title compound (88 mg).

Workup

  1. customobtained by the method
  2. distillationAfter azeotropic distillation with toluene, thionyl chloride (118 μl)
  3. additionwas added to a suspension of the residue in toluene (2 ml)
  4. stirringthe mixture was stirred at 80° C. for 16 hours and at 100° C. for 8 hours
  5. customAfter leaving
  6. temperatureto cool to room temperature
  7. extractionfollowed by extraction with ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography (developed with methanol-chloroform)

Sources & evidence

ORD record
ord-1e333bb1a62a4d04967600331383b3cf
Source dataset
uspto-grants-2013_05
Patent number
US08436012B2

Reaction notes

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