Hydrochloric Acid → imidazo[1,2-a]pyridin-6-amine

Participants

Reaction Steps

2-Amino-5-nitro pyridine was suspended in a 40 mL solution of EtOH/conc. HCl (3:1). To this suspension was added 2-bromo-1,1-dimethoxy-ethane (6.37 mL, 53.91 mmol) and the resulting mixture was heated to reflux for 8 h, after which additional 2-bromo-1,1-dimethoxy-ethane (6.37 mL, 53.91 mmol) was added. The mixture was heated at reflux overnight, cooled to rt and placed in a refrigerator for 24 h. The precipitates were collected, washed with ice-cold EtOH, air-dried and converted to the free-based using standard procedures to afford a yellow solid. The resulting crude yellow solid, (404 mg) was dissolved in 150 mL THF/MeOH (1:1) and the resulting solution was hydrogenated for 4 h over Pd/C (250 mg, 10%) using a hydrogen balloon. The mixture was filtered though Celite eluting with THF/MeOH (1:1) and the filtrate was concentrated. Purification was achieved using silica gel flash chromatography with 20% MeOH in CH2Cl2 to give Compound 846A (241 mg, 75%) as a colorless oil which turns dark upon standing.

Provenance & Evidence