Acetic Acid → 6-Bromo-1H-pyrazolo[4,3-b]pyridine

HRID 2404271Notes

Reaction equation

HRID 2404271 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9]C(=O)C)[C:5]([CH3:8])=[N:6][CH:7]=1.C([O-])(=O)C.[K+].C(O)(=O)C.C(OC(=O)C)(=O)C.C(O[N:35]=O)CC(C)C.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[NH:9][N:35]=[CH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 67151326N-(5-bromo-2-methylpyridin-3-yl)acetamide

Product 1

HCID 401522596-Bromo-1H-pyrazolo[4,3-b]pyridineYield 77%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of N-(5-bromo-2-methylpyridin-3-yl)acetamide (8.28 g, 36 mmol) in chloroform (550 mL) at ambient temperature was added potassium acetate (4.32 g, 43.6 mmol), acetic acid (2.5 mL, 43.6 mmol) and followed by acetic anhydride (6.86 mL, 72.6 mmol). The mixture was stirred at ambient temperature for 15 minutes before being heated to 40° C. Isoamylnitrite was then added dropwise. The reaction was then stirred at 60° C. for 48 hours. The reaction mixture was poured slowly into a saturated solution of sodium bicarbonate (500 mL) at 0° C. The organic phase was retained and the aqueous phase extracted with dichloromethane (500 mL). The combined organics were then concentrated to a brown oil which was dissolved in methanol (500 mL). Aqueous sodium hydroxide (2 M, 500 mL) was added at 0° C. and the mixture stirred at ambient temperature for 1 hour before the methanol was removed in vacuo. The aqueous mixture was then extracted with ethyl acetate (3×500 mL). The combined organics dried over magnesium sulfate, and the solvent removed in vacuo to give 6-bromo-1H-pyrazolo[4,3-b]pyridine as a light brown solid (5.5 g, 27.9 mmol, 77%). 1HNMR (400, CD3OD): 8 ppm 8.55 (s, 1H), 8.24 (s, 1H), 8.21 (s, 1H).

Workup

  1. temperaturebefore being heated to 40° C
  2. stirringThe reaction was then stirred at 60° C. for 48 hours
  3. extractionthe aqueous phase extracted with dichloromethane (500 mL)
  4. concentrationThe combined organics were then concentrated to a brown oil which
  5. dissolutionwas dissolved in methanol (500 mL)
  6. additionAqueous sodium hydroxide (2 M, 500 mL) was added at 0° C.
  7. stirringthe mixture stirred at ambient temperature for 1 hour before the methanol
  8. customwas removed in vacuo
  9. extractionThe aqueous mixture was then extracted with ethyl acetate (3×500 mL)
  10. dry with materialThe combined organics dried over magnesium sulfate
  11. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-04f1909ee3cb46a69d14d605c8baa561
Source dataset
uspto-grants-2014_08
Patent number
US08802690B2

Reaction notes

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