This article describes a new methodology for the parallel synthesis of 3,4-dihydroquinoxalin-2-ones containing three points of diversity. The synthesis begins with commercially available resin-bound alpha-amino acids as the source of the first diversity element and employs a combination of solid- and solution-phase chemistry to introduce the other two. The key step is an intramolecular cyclization and simultaneous traceless cleavage from the solid support to give a disubstituted 3,4-dihydroquinoxalin-2-one. The third substituent is introduced in solution by N-alkylation of the aniline nitrogen using a scavenger resin to dispose of excess reagent. All the reactions in the sequence take place at room temperature without the need to use strong acids or to maintain an inert atmosphere, thereby preserving the chiral integrity of the starting alpha-amino acid and facilitating the generation of libraries in a high-throughput parallel format.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.