N-bromobutanimide → 3-Bromo-2-methylpyrazolo[1,5-a]pyridine

HRID 2282321Notes

Reaction equation

HRID 2282321 reaction equation
[CH3:1][C:2]1[C:10](C(O)=O)=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[Br:14]N1C(=O)CCC1=O>>[Br:14][C:10]1[C:2]([CH3:1])=[N:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

3

Reactant 2

HCID 67184N-bromobutanimideHCID 128722962-Methylpyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 1

HCID 580948243-Bromo-2-methylpyrazolo[1,5-a]pyridine

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 2-methylpyrazolo[1,5-a]pyridine-3-carboxylate (5.6 g, 24 mmol) in methanol (40 mL, 1000 mmol) was added aqueous sodium hydroxide solution (5.0 mL, 8 M) and the mixture heated to 4° C. for 60 h. The reaction was allowed to cool, hydrochloric acid (5.0 mL, 12 M) and water (150 mL) was added to give a colorless precipitate. The solid was filtered, washed with water and dried in a vacuum oven to give crude 2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid, 2.63 g. A suspension of 2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid (2.0 g, 11 mmol), in Acetonitrile (120 mL) and water (60 mL) was degassed and [I,I-Bis(trifluoroacetoxy)iodo]benzene (2.90 g, 6.74 mmol) was added and the reaction heated under argon to 60 C for 15 min. Gave a clear solution. N-Bromosuccinimide (2.40 g, 13.5 mmol) was added and the solution was stirred at 60° C. for 30 minutes under an atmosphere of argon. The color turned dark. The reaction was heated for a further 30 min, allowed to cool, concentrated to remove acetonitrile and the aqueous extracted with EtOAc (3×50 ml). The organics were combined, washed with ascorbic acid solution, water, dried (MgSO4) and concentrated. The product was purified by column chromatography on silica gel eluting with DCM to 0.5% MeOH in DCM. The title compound was isolated as an off white solid, 0.56 g. LC/MS (FA) ES+ 210.9, 212.9.

Workup

  1. customin Acetonitrile (120 mL) and water (60 mL) was degassed
  2. temperaturethe reaction heated under argon to 60 C for 15 min
  3. customGave a clear solution
  4. temperatureThe reaction was heated for a further 30 min
  5. temperatureto cool
  6. concentrationconcentrated
  7. customto remove acetonitrile
  8. extractionthe aqueous extracted with EtOAc (3×50 ml)
  9. washwashed with ascorbic acid solution, water
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. customThe product was purified by column chromatography on silica gel eluting with DCM to 0.5% MeOH in DCM

Sources & evidence

ORD record
ord-3b8af3661ff74da2a92435c6e56d6108
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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