Synthesis of Heterocyclic Compounds with Pyrimidine-4-carbaldehydes as Key Intermediates

Abstract

AbstractWith the motivation to expand the compound library of specifically substituted pyrimidine derivatives, we prepared several pyrimidine-4-carbaldehydes. In most cases, the chemoselective oxidation of 4-hydroxymethyl-substituted pyrimidine derivatives could be achieved in good yields to provide the desired compounds. Alternatively, the aldehydes were prepared by Riley oxidation with selenium dioxide from the corresponding 4-methylpyrimidines. The formyl group of these compounds was employed as handle to generate alkynyl, cyano, oxazol-5-yl or β-ketoester substituents. Furthermore, two methods were found to prepare furo[3,2-d]pyrimidines. A serendipitously discovered reaction to a 6-(pyrimidin-4-yl)furo[3,2-d]pyrimidin-7-ol derivative involves a mechanistically interestingly ‘dimerization’ process with a benzoin addition as key step. Other compounds in this series contain amino, azido, or 1,2,3-triazol-1-yl groups. All these transformations to highly substituted pyrimidine derivatives demonstrate the synthetic versatility of pyrimidine-4-carbaldehydes and similar compounds.