A Novel Smiles Rearrangement Gives Access to the A-Ring Pyridine Isomers of the Nevirapine Ring System

Article abstract of DOI:10.1021/jo00077a016

The cyclization of N-methylamide 9 gives, along with the expected product 2, the isomeric diazepinone 3 resulting from a novel Smiles rearrangement in which an N-methylcarboxamide functions as a leaving group.The mechanism of the reaction has been proven by isolation of the intermediate 10 and by conducting the rearrangement on the model compound 13.The relative amounts of 2, 3, and 10 formed from 9 are subject to some control by variation of the base and reaction temperature (Table I).This new Smiles rearrangement was applied to the synthesis of the remaining two A-ring isomers 4 and 5 of the nevirapine ring system 1 by cyclization of the thioether 16 and the sulfoxide 17.