Trimethylsilyl Polyphosphate Promoted Efficient Synthesis of 4(3H)‐Quinazolinones from Methyl Anthranilate

A trimethylsilyl polyphosphate (PPSE) promoted synthesis of 4(3H)‐quinazolinones, a heterocycle with wide biological potential, from methyl anthranilate and secondary amides is described. The procedure is general, involves very easily available starting materials, shows functional group tolerance and leads to good to excellent yields. The method proved to be suitable for scaling‐up. A one‐pot approach was also explored. This step‐economic modification reduces the time, waste and environmental impact of the synthesis and leads to satisfactory global yields that include 2 or 3 single steps. Finally, a possible reaction mechanism that involves a nitrilium cation intermediate is proposed. A series of 4(3H)‐quinazolinones with variable steric and electronic features were synthesized with good to excellent yields by trimethylsilylpolyphosphate (PPSE) promoted reaction of secondary amides and methyl anthranilates. The reaction is metal and ligand free, involving easily available starting materials, and suitable for scaling up. The one pot modification, which comprises 2 or 3 steps, was also efficient.