Synthesis of 5 H-pyridazino[4,5- b]indoles and their benzofurane analogues utilizing an intramolecular Heck-type reaction

Abstract

The title ring systems were prepared from pyridazin-3(2 H)-one precursors in novel, efficient pathways. 2-Methylbenzo[ b]furo[2,3- d]pyridazin-1(2 H)-one was synthesized via a regioselective nucleophilic substitution reaction of a 2-methyl-4,5-dihalopyridazin-3(2 H)-one with phenol followed by an intramolecular Heck-type reaction. The same molecule and its 6-phenyl analogue were also prepared via reaction of 2-methyl-5-iodopyridazin-3(2 H)-one or 2-methyl-5-chloro-6-phenylpyridazin-3(2 H)-one, respectively, with 2-bromophenol or 2-iodophenol followed by Pd-catalyzed cyclodehydrohalogenation. Moreover, a new approach for the synthesis of 2-methyl-2,5-dihydro-1 H-pyridazino[4,5- b]indol-1-ones was also elaborated utilizing a Heck-type ring closure reaction on 5-[(2-bromophenyl)amino]-2-methylpyridazin-3(2 H)-ones which were obtained via Buchwald–Hartwig amination of 2-methyl-5-halopyridazin-3(2 H)-ones with 2-bromoaniline.