Imidazo(1,2-b)pyridazine, 6-chloro- → (+)-6-[(2-(S)-methyl-3-sulfamoylpropyl)thio]imidazo[1,2-b]pyridazine

Participants

Reaction Conditions

Reaction Steps

To a solution of 0.78 g of 2-(S)-methyl-3-chloro-1-propanesulfonamide in 20 ml of methanol was added 20 ml of 2N potassium hydrosulfide-ethanol solution, followed by refluxing at 70° C. for an hour in a stream of nitrogen. Further, to the mixture were added 1.0 g of 28% sodium methoxide-methanol solution and 0.73 g of 6-chloroimidazo[1,2-b]pyridazine, followed by refluxing for 3 hours. The reaction mixture was concentrated under reduced pressure. The residue to which 10 ml of water were added was adjusted to pH 6.0 with 1N-hydrochloric acid and then extracted with tetrahydrofuran-ethyl acetate (1:1). The extract was dried over anhydrous magnesium sulfate and distilled to remove the solvent under reduced pressure. The residue was subjected to a silica gel column chromatography, eluting with chloroform-methanol (10:1). The corresponding fractions were concentrated under reduced pressure to obtain 0.29 g of the title compound. This product was dissolved in 2 ml of hydrochloric acid-methanol, and the resultant was concentrated under reduced pressure. The residue was recrystallized from a mixture of methanol-ethyl ether to obtain 0.2 g of hydrochloride of the title compound.

Provenance & Evidence