One-Pot, Telescopic Approach for the Chemoselective Synthesis of Substituted Benzo[e]pyrido/pyrazino/ pyridazino[1,2-b][1,2,4]thiadiazine dioxides and Their Significance in Biological Systems

摘要

The one-pot telescopic approach has been developed for the chemoselective synthesis of substituted benzo[e]pyrido/pyrazino/pyridazino[1,2-b][1,2,4]thiadiazine dioxides using readily available 2-aminopyridines/pyrazines/pyridazine and 2-chloro benzene sulfonyl chloride. This one-pot procedure involves the chemoselective sulfonylation of 2-aminopyridines/pyrazines/pyridazine with 2-chloro benzene sulfonyl chloride followed by a Cu(I)-catalyzed Ullmann-type C-N coupling reaction to obtain benzo[e]pyrido/pyrazino/pyridazino[1,2-b][1,2,4]thiadiazine dioxides with broad substrate scope and high functional group tolerance. The synthetic sequence merges well with the nucleophilic attack on the 2-amino group of pyridines/pyrazines/pyridazines on the 2-chloro benzene sulfonyl chloride, followed by Cu(I)-catalyzed ipso chloro displacement to C-N bond formation resulting in a more modular and straightforward approach. Moreover, the biological significance of the synthesized benzothiadiazine dioxides was evaluated by following their ability to bind to protein macromolecules and their anti-inflammatory activity.