An Efficient Synthesis of Some 6‐Substituted 4,8‐Diaza‐3,3,9,9‐ tetramethylundeca‐2,10‐dione Dioximes (Propylene Amine Oximes, PnAOs): Ligands for 99mTc Complexes Used in Structure Distribution Relationship (SDR) Studies.

Abstract Technetium complexes of the ligand PnAO [4,8-diaza-3,3,9,9-tetramethylundeca-2,10-dione dioximes (3)] are of interest as commercial radiopharmaceuticals. In general, PnAOs are synthesized by alkylation of a propylenediamine derivative with 3-chloro-3-methyl-2-nitrosobutane (2). This alkylation reaction proved to be low yielding. With modestly bulky substituents at the 2-position of 1,3-diaminopropane, little or none of the required PnAO was obtained. As a result, an alternative approach of the synthesis of PnAO was developed. This method involved the alkylation of the propylenediamine with 3-bromo-3-methylbutan-2-one (18) followed by oximation of the resulting diamine-diketone (19). By this method, PnAOs were prepared in good yield, even with bulky C-2 substituents. Fourteen PnAO derivatives were prepared by this method. We also describe the syntheses of several new propylenediamine derivatives.