Copper-free Route to Triazole-Modified Peptidomimetic by the Combination of Two Multicomponent Reactions in One Pot

An efficient copper-free protocol for the synthesis of 5-methyl-1H-1,2,3-triazole-modified peptidomimetics through the combination of Ugi four-component reaction with a three-component cycloaddition, has been developed. The copper-free straightforward process is suitable for drug discovery. The chemoselective preparation of 1,4-disubstituted, triazole-modified peptidomimetics by using alkynyl substituted amines may have potential biological and synthetic application. At last, a "Lapinski type" analysis of the physical properties was performed, which is expected to help drug discovery.