Acetic Anhydride → 1-(1H-pyrazolo[4,3-b]pyridin-1-yl)ethanone

HRID 246051Notes

Reaction equation

HRID 246051 reaction equation
[NH2:1][C:2]1[C:3]([CH3:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:9]([O:12]C(=O)C)(=O)[CH3:10].C([O-])(=O)C.[K+].[N:21](OCCC(C)C)=O>C(Cl)(Cl)Cl>[N:1]1([C:9](=[O:12])[CH3:10])[C:2]2[C:3](=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:8]=[N:21]1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 5726163-Amino-2-methylpyridine

Product 1

HCID 450862101-(1H-pyrazolo[4,3-b]pyridin-1-yl)ethanoneYield 65.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 3-amino-2-methylpyridine (1.0 g, 9.25 mmol) in CHCl3 (24 ml) at 0° C. was slowly added acetic anhydride (2.0 ml, 21.3 mmol). The reaction mixture was warmed to room temperature and stirred for 1 h. Potassium acetate (272 mg, 2.77 mmol) was added followed by slow addition of isoamyl nitrite (2.7 ml, 19.9 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was dissolved in EtOAc and washed with water, sat'd NaHCO3 and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane to give 973 mg (65%) of 1-pyrazolo[4,3-b]pyridin-1-yl-ethanone as a light yellow solid.

Workup

  1. customat 0° C.
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux overnight
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with water
  8. dry with materialthen dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-4aa0f06762cb497ea0010e80e63bd29b
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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