An Improved Route to the Regioselective Synthesis of 1,7-dibenzyl-1,4,7,10-tetraazacyclododecane

Abstract

Abstract 1,7-dibenzyl-1,4,7,10-tetraazacyclododecane is a crucial intermediate in the preparation of tetra-armed 1,4,7,10-tetraazacyclododecane (two benzyl groups at N1- and N7- positions and two other aromatic groups at N4- and N10- positions), 1,7-disubstituted-1,4,7,10-tetraazacyclododecane, and DO2A metal chelators, which find widespread use in medicine. Current frequently-used synthesis is costly and involves multi-steps under harsh reaction conditions, delivering low yields. We present a simpler, highly regioselective synthesis of the 1,7-dibenzyl-1,4,7,10-tetraazacyclododecane that operates under mild reaction conditions.