Copper(I)-Catalyzed\nIntramolecular Tandem Acylation/<i>O</i>‑Arylation\nunder Mild Conditions: Synthesis of Benzofuro[3,2‑<i>c</i>]quinolin-6(5<i>H</i>)‑ones and G‑Quadruplex-Targeting\nAnalogues

This paper presents\na copper(I)-catalyzed intramolecular tandem\nacylation/<i>O</i>-arylation of methyl 2-[2-(2-bromophenyl)acetamido]benzoates\nfor the synthesis of benzofuro[3,2-<i>c</i>]quinolin-6(5<i>H</i>)-ones under mild conditions. The combination of CuI, 1,10-phenanthroline,\nand K<sub>2</sub>CO<sub>3</sub> in DMSO was found to be the optimal\nreaction condition, producing the target products in high yields (84–99%)\nat 70 °C for 16 h. The tandem reaction was applicable to substrates\nbearing halo, electron-withdrawing, and electron-donating groups at\ntheir phenyl moieties with a broad substrate scope. Further derivation\nproduced compounds serving as G-quadruplex DNA (G4 DNA) stabilizers.\nThe most potent analogue, 2,9-bis{[3-(diethylamino)propyl]amino}-5-methylbenzofuro[3,2-<i>c</i>]quinolin-6(5<i>H</i>)-one, significantly increased\nthe melting temperature of G4 DNA by 9.8 °C at 1.0 μM,\napproximately 4.6 times more selective than duplex DNA. The G4 stabilizer\nalso showed anticancer activity, actively inhibiting MDA-MB-231 cancer\ncells with a GI<sub>50</sub> value of 0.41 μM.