Synthesis of cis-fused hexahydro-4aH-indeno[1,2-b]pyridines via intramolecular Ritter reaction and their conversion into tricyclic analogues of NK-1 and dopamine receptor ligands

Indanol intermediates prepared via Michael addition of 1-indanone β-ketoester and acrylonitrile, followed by Grignard reaction of the ketone group, were submitted to an intramolecular Ritter reaction to produce cis-fused methyl 2-oxo-9b-phenyl-1,2,3,4,5,9b-hexahydro-4aH-indeno[1,2-b]pyridine-4a-carboxylates with 4a,9b-diangular substitution pattern. Further transformation of the bridgehead ester group and the lactam function afforded constrained tricyclic analogues of some monocyclic piperidine NK-1 antagonists and of a bicyclic dopamine receptor ligand.