Acetonitrile as a solvent, excess of primary amines as general bases, and a reflux condition make the multi-component reactions of (2-cyanoacetyl) carbamate 1, ethyl orthoformate, and primary amines form 5-cyanouracils 4a–c feasibly. Mechanistic studies of the multi-component reaction were carried out by proton NMR spectrometer. Acetonitrile as a solvent makes the reaction of 1 with ethyl orthoformate produce E-ethyl (2-cyano-3-ethoxyacryloyl) carbamate E-2 without a catalyst of acetic anhydride. The reactions of E-2 with primary amines produce the corresponding Z-3a–c as the only stable isomers eventually in CDCl 3 or CD 3 CN. General-base-catalyzed intramolecular cyclizations of Z-3a–c at a reflux condition in CD 3 CN generated the corresponding 5-cyanouracils 4a–c.