Efficient Synthesis of New C-Functionalized Macrocyclic Polyamines

A powerful synthetic route for the preparation of new polyazamacrocycles, valuable precursors of bifunctional chelating agents with applications in nuclear medicine, is reported. The desired functional group was introduced onto the macrocycle backbone during the cyclization step, thus avoiding the tedious preparation of a C‐functionalized synthon. The regioselective reaction of macrocycles bearing an aminomethyl pendant arm with aldehydes is also described. We report a very convenient synthesis of cyclen and [13]aneN4 derivatives bearing an aminomethyl pendant group on a carbon atom. The cyclization step is performed by using chloroacetaldehyde and benzotriazole. The benzotriazole moiety is then replaced by a nitrile group, which is reduced to yield the target compounds. Such macrocycles can be further functionalized to give bifunctional chelatingagents.