6-Bromo-imidazo[1,2-a]pyridine-8-carboxylic acid

Synthesis

97-97-2

52833-94-0

903129-78-2

GENERAL STEPS: 2-Amino-5-bromonicotinic acid (5.0 g, 23.04 mmol) and sodium acetate (3.78 g, 46.1 mmol) were dissolved in 100 mL of a 60% aqueous ethanol solution under stirring conditions. Subsequently, a solution of 2-chloro-1,1-dimethoxyethane (5.74 g, 46.1 mmol) in water (6 mL) was added to this solution and concentrated hydrochloric acid (1.0 mL) was added dropwise. The reaction mixture was heated to reflux for 2.5 hours. Upon completion of the reaction, the solvent was removed under reduced pressure and the residue was diluted with cold water and the pH adjusted to neutral (about 7) with saturated sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate (2 x 100 mL), the organic phases were combined, washed sequentially with water (2 x 100 mL) and brine (2 x 100 mL) and dried over anhydrous sodium sulfate. The crude product was purified by grinding with petroleum ether containing 2% ethyl acetate. 4.8 g of 6-bromoimidazo[1,2-a]pyridine-8-carboxylic acid was obtained in 86% yield. The product characterization data were as follows: 1H NMR (DMSO-d6, 300 MHz): δ 7.66 (d, 1H, J = 1.2 Hz, Ar), 7.79 (d, 1H, J = 1.5 Hz, Ar), 8.04 (s, 1H, Ar), 8.96 (d, 1H, J = 1.5 Hz, Ar); MS (ES+): m/e 242 (M + 1 ).

References