Liquid phase parallel synthesis of guanidines

Combinatorial synthesis of N,N′-di(Boc)-Protected guanidines containing piperazine and pyrrolidine scaffolds has been developed. We initiate a preliminary study on the reactivity of several guanylating reagents with soluble polymer-bound diamines in liquid phase. Guanidines are liberated from the polymer support under mild conditions in high yields and high purity by simple precipitation and washings. This combinatorial liquid-phase methodology proves to be a useful tool for constructing guanidine libraries containing diamine scaffolds.