Towards New Tricyclic Motifs: Intramolecular C–H Arylation as the Key Step in a Formal [3+3] Cyclocondensation Strategy

Tricyclic scaffolds structurally related to the wellknown benzodiazepine class of drugs show diverse biological activities strikingly different from those of their benzodiazepine counterparts. Interested by this scaffold-hopping perspective, we previously developed a continuous-flow method for the conversion of benzodiazepinediones into oxazoloquinolinones. Attempted extension of this synthetic route to the corresponding oxazolonaphthyridinone scaffolds met with limited success, however. This encouraged us to develop a different approach to pyridine-based tricyclic motifs. In line with our interest in scaffold hopping, in this paper we describe a general, convergent [3+3] cyclocondensation approach to [1,3] oxazolo[4,5-c]1- naphthyridin-4(5H)-ones. The key synthetic steps in this approach are: (1) the construction of an amide linkage connecting two peripheral heterocycles; and (2) a palladium-catalysed intramolecular C-H arylation to complete the tricyclic scaffold.