A method for the high efficiency of water-soluble carbodiimide-mediated amidation.

Water-soluble carbodiimides are widely used for carboxyl-amine conjugation. However, extremely variable and low yields, obtained under a variety of conditions, have been a serious problem in the coupling. A simple method, optimizing various parameters of the coupling reaction, in which N-hydroxysuccinimide is included to assist the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-catalyzed amidation reaction is described. A product yield of up to 90% is routinely achieved.