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

Participants

Reaction Steps

Into a 500 mL four-necked separable flask purged with nitrogen, 20.17 g of 2,6-dichloroimidazo[1,2-b]pyridazine (content: 99.2% by weight) and 190.5 g of xylene were charged to prepare a xylene solution containing 2,6-dichloroimidazo[1,2-b]pyridazine. The solution obtained by mixing 4 mL of xylene and 0.22 g of 1,3-bis(diphenylphosphino)propane and 0.62 g of a toluene solution of nickel naphthenate (II) (content: 5% by weight) were mixed to prepare a solution containing a nickel catalyst. The xylene solution containing 2,6-dichloroimidazo[1,2-b]pyridazine and the solution containing a nickel catalyst were mixed, and to the resultant mixture, 63.4 g of a tetrahydrofuran solution of n-propylmagnesium bromide (content: 22.2% by weight) was added dropwise over about 2 hours at an inner temperature of 20 to 30° C. to effect reaction. After completion of the reaction, the reaction mixture was added dropwise into a mixture of 40.4 g of 3% by weight aqueous sulfuric acid solution and 1 g of Radiolite (which was manufactured by Showa Chemical Industry Co., LTD.). After that, the resultant mixture was stirred and filtrated. The organic layer was separated from the filtrate obtained and washed twice with about 40 g of water. The organic layer after washing was concentrated to obtain 20.9 g of 6-n-propyl-2-chloroimidazo[1,2-b]pyridazine (purity: 93.2%). Yield: 94%

Provenance & Evidence