8-Bromo-imidazo[1,2-a]pyridine

Synthesis

The general procedure for the synthesis of 8-bromo-imidazo[1,2-A]pyridine from chloroacetaldehyde and 2-amino-3-bromopyridine was as follows: 2-amino-3-bromopyridine (5.00 g, 28.9 mmol) was dissolved in ethanol (100 mL), and sodium bicarbonate (3.64 g, 43.3 mmol) and 2-chloroacetaldehyde (7.1 mL, 43 mmol) were added sequentially. The reaction mixture was heated under reflux conditions with stirring for 4 hours. Upon completion of the reaction, the mixture was allowed to cool to room temperature and the solvent was subsequently removed by evaporation under reduced pressure. Water was added to the residue and extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluent ratio: n-hexane/ethyl acetate=70:30→40:60) to afford the target compound 8-bromoimidazo[1,2-a]pyridine (5.71 g, quantitative yield).

References

[1] Patent: EP3351533, 2018, A1. Location in patent: Paragraph 0524
[2] Patent: JP2018/145180, 2018, A. Location in patent: Paragraph 0490
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 21, p. 9089 - 9106,18
[4] Patent: WO2016/206101, 2016, A1. Location in patent: Page/Page column 84