Synthesis of three metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine. A new rearrangement of 3-[1-methylethyliden)hydrazino] derivative.

The synthesis of three metabolites (I), (II), (III) , isolated from rat urine, of the hypotensive compound 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydrochloride (IV), is described. The first metabolite, 3-[bis-(2-hydroxyethyl)amino]pyridazine (I) (Scheme 1) was obtained either by reaction of 6(3)-chloro-3(6)-[bis-(2-hydroxyethyl)amino]pyridazine-N-oxide (V) with hydrazine hydrate or by catalytic hydrogenation of 3-chloro-6-[bis(2-hydrxyethyl)amino]pyridazine (VI). 3-Methyl-6-[bis-(2-hydroxyethyl)amino]-2-triazolo [4,3-b]pyridazine (II) was prepared (Scheme 2) by reaction of (IV) with acetic anhydride and subsequent hydrolysis of the resutling 6-[bis-(2-acetyloxyethyl)amino]-s-triazolo[4,3-b]pyridazine (VII). The third metabolite, 3-[bis-(2-hydroxyethyl)amino]-6-isopropyloxypyridazine (III) Scheme 3), was synthesized from 3-[(1-methylethyliden)hydrazino]-6-[bis-(2-hydroxyethyl)amino]pyridazine (VIII) which in phosphate buffer (pH 7.38) or in sodium hydrogen carbonate solution, underwent a rearrangement of new type to give (III).