A novel one-pot practical approach for the preparation of isocyanide directly from amine and its reaction has been developed. It employs formylation of amine, dehydration of formamide to isocyanide, and its multicomponent reactions (Ugi, Passerini, and Groebke–Blackburn–Bienaymé reactions). This method provides a significant solution to known synthetic difficulties of isocyanides. In this approach, the nature and stoichiometric quantities of dehydrating agent and base, and the catalysis-function of by-products were found to play crucial roles.