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-5H-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.