Hydrochloric Acid → 2-Chloro-6-propylimidazo[1,2-b]pyridazine

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Reaction Steps

2,6-Dichloroimidazo[1,2-b]pyridazine (10.0 g, 53.2 mmol) and [1,3-bis(diphenylphosphino)propane]nickel (II) dichloride (0.43 g, 0.80 mmol) were added to tetrahydrofuran (80.0 ml) under a nitrogen stream, and a solution of n-propylmagnesium bromide in tetrahydrofuran (2 M, 31.9 ml, 63.8 mmol) was added dropwise over 60 minutes to the mixture under ice-cooling. The mixture was stirred for 10 minutes under ice-cooling, and the reaction mixture was warmed to room temperature and stirred for 2 hours at room temperature. Cold water (700 ml) was added to the reaction mixture which was then acidified with conc. hydrochloric acid, and the precipitated solids were collected by filtration, and the insoluble solids were washed with dilute hydrochloric acid and then with water. On one hand, the filtrate was extracted with ethyl acetate, and the extracts were combined and washed with dilute hydrochloric acid, a saturated saline solution, an aqueous saturated sodium bicarbonate solution and a saturated saline solution in this order. The resulting organic layer was dried over anhydrous magnesium sulfate, filtrated and concentrated. The concentrated residues and the solids collected by filtration were purified by silica gel column chromatography (ethyl acetate:hexane=3:7), to give the title compound as white crystals. The yield was 9.21 g (88.5%).

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