Solid-phase synthesis of trisubstituted 2-imidazolidones and 2-imidazolidinethiones

An efficient method for the solid-phase synthesis of 1,3,4-trisubstituted-2-imidazolidones and 1,3,4-trisubstituted-2-imidazolidinethiones from reduced N-acylated dipeptides is described. The complete reduction of the amide bonds of an N-acylated dipeptide with borane in THF results in two secondary and one tertiary amine. Reaction of the resulting resin-bound polyamine 4 with carbonyldiimidazole or thiocarbonyldiimidazole affords, respectively, cyclic ureas 6 and cyclic thioureas 7 in high yield and purity. Details on the selection of the building blocks and characterization of the controls for the libraries' synthesis will be presented. These procedures have also been used to generate parallel arrays and mixture-based combinatorial libraries of cyclic ureas and thioureas.