Chloroacetaldehyde → 2-Chloroimidazo[1,2-b]pyridazine

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Reaction Conditions

Reaction Steps

Chloro-imidazo[1,2-b]pyridazine (10-1) was synthesized as shown in scheme 10, wherein chloracetaldehyde (55% in water, 126 ml, 880 mmol) was added to a solution of 6-chloro-pyridazin-3-ylamine (25.43 g, 196 mmol) and NaHCO3 (28 g, 334 mmol) in EtOH (600 ml) and then the reaction mixture was heated to reflux while stirring for 14 hours. The resulting dark brown reaction mixture was then concentrated under vacuum and the resulting residue reconstituted with dichloromethane (DCM). This solution was filtered through a celite pad and the solid washed with DCM and the solvent was then removed to yield a dark brown oil. 2M HCl (290 ml) and water (300 ml) was added to the residue and the resulting slurry was stirred at room temperature for 15 minutes. The solution was filtered through a celite pad and the filter cake was washed with water. The filtrate was extracted with diethyl ether (3×200 ml). The aqueous layer was cooled to 0° C. (ice bath) and neutralized using NaOH (24 g). The resulting slurry was extracted with diethyl ether (6×300 ml), dried using sodium sulfate and the diethyl ether was removed using a rotary evaporator to yield chloro-imidazo[1,2-b]pyridazine (10-1) as a light orange solid. MS: 155.1 [M+1]+.

Provenance & Evidence