Towards novel tricyclic motifs: intramolecular C-H arylation as the key step in a formal (3+3) cyclocondensation strategy

Tricyclic scaffolds, structurally related to the well known benzodiazepine drug class, show diverse and strikingly different biological activities than their benzodiazepine counter parts. Interested by this scaffold hopping perspective, we previously developped a continuous flow method converting benzodiazepinediones to oxazoloquinolinones. Exploration of this synthetic route to the corresponding oxazolonaphthyridinone scaffolds met with limited success however, encouraging us to develop a different approach for pyridine based tricyclic motifs. In line with our interest in scaffold hopping, herein we describe a general, convergent (3+3) cyclocondensation approach giving access 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 link connecting two peripheral heterocycles and (2) a palladium-catalysed intramolecular C-H arylation completing the tricyclic derivative.

Publication year:2017

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BOF-publication weight:1

CSS-citation score:1

Authors from:Higher Education

Accessibility:Open