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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence