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.(c) 2023 Elsevier Ltd. All rights reserved.

Automated summary

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 react efficiently with N-, S-, O- and C-nucleophiles, providing the corresponding disubstituted pyridopyrimidinone products in good yields. This method is simple and avoids the use of transition metals, allowing for rapid assembly of this structural motif for SAR studies and late stage process development.