Efficient and metal Free synthesis of 2,3-disubstituted pyridopyrimidinones via ketenimine intermediates

A highly efficient synthesis has been developed for the direct access of 2,3-disubstitued 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. [Display omitted]