3,6-Dichloroimidazo[1,2-b]pyridazine

Synthesis

6775-78-6

40972-42-7

6-Chloroimidazo[1,2-b]pyridazine (6.53 mmol) was used as starting material, which was dissolved in chloroform (12 mL) and N-chlorosuccinimide (6.53 mmol) was added under nitrogen protection. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the mixture was partitioned between saturated sodium bisulfate solution (25 mL) and chloroform (12 mL). The organic layer was separated, washed with water (2 x 12 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 3,6-dichloroimidazo[1,2-b]pyridazine (1.05 g, 85% yield) as an orange solid. The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 7.92 (d, J = 9.5 Hz, 1H), 7.74 (s, 1H), 7.12 (d, J = 9.5 Hz, 1H). 3,6-Dichloroimidazo[1,2-b]pyridazine (150 mg, 0.8 mmol) was placed in a sealed tube with the corresponding amine (1 mL) and heated at 120 °C for 16 hours. At the end of the reaction, it was cooled to room temperature and the reaction mixture was concentrated under reduced pressure. Purification by column chromatography (using a 12 g ISCO column with the eluent being a solvent mixture of dichloromethane and ammonia-containing methanol (10:1) at a flow rate of 25 mL/min with a gradient elution from 100% dichloromethane to 80% dichloromethane over a period of 30 min) yielded the target product 6.

References