ABSTRACT
Amide bond formation is one of the most valuable tools used to construct drug molecules. N,Ncarbonyldiimidazole (CDI) as a coupling agent for amide bond formation is increasingly applied to the large-scale synthesis of a number of pharmaceutical products, for example, sildenal,2 darifenacin,3 and sunitinib.4 The evolution of a carbon dioxide by-product provides a driving force for the reaction. In addition, the imidazole by-product can be removed by acidic wash. A disadvantage of using CDI is that the resulting imidazolide intermediate is less reactive than the corresponding acid chloride. Consequently, CDI-mediated amide bond formation often requires a catalyst to promote the reaction.
