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

Participants

Reaction Steps

6-Chloroimidazo[1,2-b]pyridazine 41 (6.53 mmol) was dissolved in chloroform (12 mL) and N-chlorosuccinimide (6.53 mmol) added under N2. After stirring for 16 h, the mixture was partitioned between saturated sodium hydrogensulfate solution (25 mL) and chloroform (12 mL). The organic layer was removed, washed with water (2×), dried and concentrated to provide 3,6-dichloroimidazo[1,2-b]pyridazine 5 (1.05 g, 85%) as an orange solid; 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 5 (150 mg, 0.8 mmol) and the desired amine (1 mL) were heated in a sealed tube for 16 hr at 120° C. Upon cooling the reaction mixture was concentrated and purified by column chromatography (12 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 80% methylene chloride over 30 min at 25 mL/min) to provide the desired product 6.

Provenance & Evidence