Efficient & Metal-Free Synthesis of 2,3-Disubstituted Pyridopyrimidones via Ketenimine Intermediates

A highly efficient synthesis has been developed for the direct access of 2,3-disubstituted 4H-pyrido[1,2-a] pyrimidin-4-ones from N-pyridoketenimine precursors.

The ketenimine intermediates are demonstrated to react efficiently with N-, S-, O– and C-nucleophiles, and provide the corresponding disubstituted pyridopyrimidinone products in good yields. This one-pot method is operationally simple and avoids the use of transition metals, enabling rapid assembly of this type of structural motif for SAR studies as well as late-stage process development.