To provide an improved synthetic pathway for the facile generation of tetraazamacrocycle(s).

Improved methods for synthesizing bifunctional chelates of tetraazamacrocycle derivatives and intermediates thereof are disclosed as well as novel tetraazamacrocycle derivatives and intermediates thereof. One aspect of the present invention is a process for alkylating the free macrocyclic nitrogen of a tris-N-substituted tetraazamacrocycle (1) to yield a tetra-N-substituted tetraazamacrocycle (2) in the presence of a weak base. Another aspects of the present invention are certain tetra-N-substituted tetraazamacrocycles (2) which may be produced in this reaction. These products are useful intermediates for generating bifunctional chelates for imaging and treatment of diseased tissues.