DNA-Compatible Benzotriazinone Formation through Aryl Diazonium Intermediates

The incorporation of N-containing heterocycles with potential bioactivity into DNA-encoded chemical libraries (DELs) represents an important approach to synthesizing medicinally useful compound collections for high-throughput screening. Herein, we reported a synthetic methodology to afford a benzotriazinone core as a drug-like scaffold in a DNA-compatible manner through aryl diazonium intermediates. Starting from DNA-conjugated amines, anthranilic acid or isatoic anhydride building blocks were coupled to form chemically diversified anthranilamides, which were subsequently transformed into 1,2,3-benzotriazin-4(3H)-one via tert-butyl nitrite-triggered cyclization. This methodology features DEL synthesis compatibility through a mild diazonium intermediate mechanism, allowing late-stage decoration of the bioactive benzotriazinone cap on DNA-conjugated amines. The broad substrate scope and high conversion render this methodology a promising approach to diversifying and decorating DNA-encoded combinatorial peptide-like libraries with medicinally relevant heterocyclic moieties.