A novel and convenient method for the synthesis of new derivatives of pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione

Abstract A novel methodology has been developed for the efficient synthesis of 1,4-pyridopyrrolodiazepine derivatives. The key reaction is the bromination under mild conditions by NBS of compounds resulting via peptide coupling of l -proline methyl ester with 3-aminopyridine-2-carboxylic acid 1 , then intramolecular cyclization in the construction of 2-bromo-6a,7,8,9-tetrahydro-5 H -pyrido[3,2- e ]pyrrolo[1,2- a ][1,4]diazepine-6,11-dione 4 . This latter is then engaged in cross-coupling reactions to generate 1,4-pyridopyrrolodiazepines derivatives 5a – m , 6a – i , 7 , and 8a – c . This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.