Regioselective Late Stage Functionalization of 2 Substituted Quinoxalines

Quinoxaline derivatives constitute a relevant class of heterocycles in medicinal chemistry.^1,2 Selective functionalization of this core remains a synthetic challenge, particularly when aiming to diversify preexisting scaffolds via late‑stage functionalization strategies.^3,4 In this work, we evaluated synthetic approaches directed at the regioselective modification of positions 3 and 7 in 2‑substituted quinoxaline derivatives, prioritizing technologies that simplify experimental execution and improve the processes' sustainability profile. Functionalization at position 3 was achieved through ortho‑directed metalation using lithium bases in the presence of ZnCl₂, which enabled subsequent synthetic derivatizations. Access to position 7 was accomplished by optimized regioselective halogenation,⁵ providing versatile precursors for downstream transformations. The developed protocols displayed promising selectivity and yields, demonstrating applicability to functionalized derivatives and potential for scale‑up.