Synthesis and Antihypoxic Activity of New 1,4-Benzodioxane Derivatives Containing a Thiazole Fragment

The Grignard reaction of 4-(1,4-benzodioxan-6-yl)tetrahydro-2H-pyran-4-carbonitrile with methylmagnesium iodide gave 1-[4-(1,4-benzodioxan-6-yl)tetrahydro-2H-pyran-4-yl]ethanone which was brominated to obtain the corresponding bromomethyl ketone. The cyclization of the latter with thiourea afforded 4-[4-(1,4-benzodioxan-6-yl)tetrahydro-2H-pyran-4-yl]-1,3-thiazol-2-amine which was acylated with substituted benzoyl chlorides, as well as with formic acid in the presence of acetic anhydride. The N-formyl derivative was reduced with lithium tetrahydridoaluminate to N-methyl-4-[4-(1,4-benzodioxan-6-yl)tetrahydro-2H-pyran-4-yl)-1,3-thiazol-2-amine. The synthesized compounds were evaluated for their antihypoxic activity.