An efficient method for the solid-phase synthesis of N, N′-substituted acylguanidines is presented. The key-step involves the N-acylation of resin immobilized S-methylisothiourea with a variety of carboxylic acids using PyAOP as the coupling agent. The resulting resin bound N-acyl-derivatives are reacted with a host of amines and the N-acyl, N′-alkyl (aryl) guanidines liberated from the resin upon exposure to TFA.
