Theoretical characterization of two reaction pathways for the intramolecular cyclization of 2-(3-benzylaminopropanoylamino)benzamide

During the investigation of the microwave synthesis of compounds related to benzodiazepines by Howard and co-workers, another group of compounds was isolated. First believed to be bicyclic amidines, these compounds were later found to be 4-quinazolinones. In this work, the potential energy surface of the precursor to the observed 4-quinazolinone is explored. The most stable arrangement is found to be a linear conformation of the side chain with the amide group in the Z conformation. Using this structure as the starting point, the reaction pathways for the intramolecular cyclization to form either the 4-quinazolinone or the bicyclic amidine are characterized.