A Concise Flow Synthesis of the IKZF2 Glue Degrader DKY709

DKY709, a protein degrader targeting Helios (IKZF2), was efficiently synthesized via flow chemistry. The synthetic sequence comprised a visible-light-induced benzyl bromination, an amination–cyclization cascade, a photoinduced C(sp2)–C(sp3) coupling, and a high-temperature, high-pressure de-Boc/alkylation. Each reaction was systematically optimized under continuous-flow or stop-flow conditions to identify crucial parameters. The overall yield was substantially increased from 4.3% to 22.8% using commercially available starting materials, while the number of synthetic steps was reduced from five to four. The scalability of each reaction step was validated, and the direct use of intermediates in subsequent steps minimized workup complexity.