126202-06-0

504-29-0

79-11-8

126202-06-0

1. dissolve chloroacetic acid: add triethylamine (6.12 mL, 44 mmol) dropwise to water (6 mL) at room temperature and stir until chloroacetic acid (3.67 g, 38.8 mmol) is completely dissolved. 2. addition of 2-aminopyridine: 2-aminopyridine (4.3 g, 46 mmol) was added to the above solution, the reaction mixture was heated to 90 °C and refluxed for 5 hours. 3. Precipitation of Intermediate 2a: After completion of the reaction, cooled to room temperature, ethanol was added and the precipitate was precipitated by stirring at 5 °C for 2 hours. Filtered, washed with cold ethanol (4 mL) and dried to give Intermediate 2a (5.3 g, 89% yield). 4. Dissolve Intermediate 2a: Intermediate 2a (5.3 g, 34.8 mmol) was dissolved in toluene (25 mL). 5. Dropwise addition of phosphorus trichloride: Under reflux conditions, phosphorus trichloride (9.7 mL, 104 mmol) was added dropwise to the above solution and reflux was continued for 16 hours. 6. Post-treatment: After completion of the reaction, cool to room temperature, add cold water (100 mL) and stir for 15 minutes. Separate the aqueous layer, neutralize with 10% NaOH aqueous solution and filter the precipitate precipitated. The precipitate was dissolved in dichloromethane and the aqueous phase was extracted with dichloromethane (4 x 20 mL). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a brown powder. 7. Purification: Purified by silica gel column chromatography using hexane:ethyl acetate (90:10) as eluent to obtain 2-chloroimidazo[1,2-a]pyridine (3a) (5.2 g, 98% yield). Note: 2-chloro-7-methylimidazo[1,2-a]pyridine (3b) can be prepared by the same method by substituting 2-amino-4-methylpyridine for 2-aminopyridine.