A protocol for the single-step synthesis of pyrimidine derivatives by condensation of N-vinyl or N-aryl amides with nitriles is described. Gram-scale synthesis of 4-tert-butyl-2-phenyl-7,8-dihydro-6H-pyrano[3,2-d]pyrimidine serves as a representative procedure for this methodology for azaheterocycle synthesis. This chemistry involves amide activation with trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine and the necessary nitrile. Nucleophilic addition of the nitrile to an activated intermediate followed by annulation affords the pyrimidine product in a single step. The total time necessary for the completion of this procedure is approximately 3 h. This chemistry has been applied to a wide range of amides and nitriles including optically active derivatives.