An unprecedented approach to 4,5-disubstituted pyrimidine derivatives by a ZnCl(2)-catalyzed three-component coupling reaction.

We have developed a ZnCl(2)-catalyzed three-component coupling reaction involving a variety of functionalized enamines, triethyl orthoformate, and ammonium acetate, which leads to the production of 4,5-disubstituted pyrimidine derivatives in a single step. The procedure can be successfully applied to the efficient synthesis of mono- and disubstituted pyrimidine derivatives, using methyl ketone derivatives instead of enamines.