2-Thiazolo[4,5-][1,2,3]triazole: synthesis, functionalization, and application in scaffold-hopping

• Published in: Chemical science (Cambridge) 2024-10, Vol.15 (38), p.15835-1584
• Main Authors: Miyazaki, Ryuya, Takada, Fumito, Kikuchi, Takunari, Oguro, Yuya, Kamata, Makoto, Yukawa, Takafumi, Kato, Kenta, Muto, Kei, Yamaguchi, Junichiro
• Format: Article
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d4sc03874f

This manuscript unveils the synthesis of 2 H -thiazolo[4,5- d ][1,2,3]triazole (ThTz), an unprecedented [5-5]-fused heteroaromatic system, and established a scalable synthetic procedure for producing large quantities of the ThTz ring bearing a sulfone group on the thiazole ring. The sulfone moiety proves to be a versatile reactive tag, facilitating diverse transformations such as S N Ar reactions, metal-catalyzed couplings, and radical-based alkylations. Furthermore, functionalization of the triazole ring highlights the potential of this newly developed heteroaromatic compound as a valuable heteroaryl building block, promoting scaffold hopping strategies in medicinal chemistry. We have developed 2 H -thiazolo[4,5- d ][1,2,3]triazole (ThTz), an unprecedented [5-5]-fused heteroaromatic system for medicinal chemistry. C5-sulfonylated ThTz has been commercialized through Tokyo Chemical Industry Ltd (TCI: catalogue number M3881).