5-Bromoimidazo[1,2-a]pyridine-2-carbaldehyde

19798-81-3

921-03-9

878197-68-3

General procedure: 2-amino-6-bromopyridine (3.0 kg, 17.3 mol) and dimethoxyethane (12 L) were added to the reactor under nitrogen protection and mixed with stirring. Subsequently, 1,1,3-trichloroacetone (5.6 kg, 30.3 mol) was added to the reaction solution at 25 °C in a single addition. The reaction system was slowly warmed to 65 °C (jacket temperature) and maintained at this temperature for 2 to 4 hours until the reaction was confirmed complete by TLC or HPLC monitoring. Upon completion of the reaction, the system was cooled to 10 °C, maintained for 1 h and filtered. The solid product was washed with dimethoxyethane (6 L). The solid was repositioned in the reactor, dimethoxyethane (12 L) and 2N hydrochloric acid (12 L) were added, and the reaction was warmed to 75 °C for 16 to 20 hours or until the reaction was complete. The reaction solution was cooled to 10 °C and the pH was adjusted to 8 with 3N sodium hydroxide solution. the solid product was collected by filtration and washed with water. Finally, the solid was dried at 50 °C for 16 h to give 5-bromoimidazo[1,2-a]pyridine-2-carbaldehyde (2.81 kg, 72% yield). The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-D6): δ 10.05 (s, 1H), 8.66 (s, 1H), 7.72 (s, 1H), 7.42 (s, 1H), 7.35 (s, 1H).