In order to achieve atom economy, efficiency, diversity, and step economy, tandem cyclization could be an efficient strategy for the systematic development of heterocycles in multi-component reactions (MCRs). In this regard, we were interested in the [2+2+2] cycloaddition reaction for the synthesis of 4-aminoquinoline. Herein, we developed copper-catalyzed regiocontrolled three-component reaction allowing systematic functionalization of 4-aminoquinoline using nitrile, iodonium salt and N-benzyl-N-mesylynamide. Furthermore, we explored base-promoted full deprotection of 4-aminoquinolines with potassium butoxide (KO^tBu) and 1,3-rearrangement of 4-aminoquinoline with lithium bis(trimethylsilyl)amide (LIHMDS) to provide quinolin-4-ylmethanesulfonamides. Finally, active antimalarial compound CK-2-68^[1] was successfully prepared by our synthetic method.


References
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