Synthesis of the HIF-2α translation inhibitor compound 76 via a Japp-Klingemann coupling

Abstract The Iliopoulos laboratory previously reported the discovery of compound 76 , a small molecule HIF2α inhibitor. HIF2α activation is known to play a critical role in both von Hippel-Lindau (VHL) disease-related tumors and sporadic renal cell carcinoma (RCC). We required a facile and scalable synthetic route to confirm the structure, to investigate the biological properties of compound 76 , and to perform structure activity relationship optimization studies. Herein, we report the straightforward synthesis of compound 76 and a preliminary investigation into the scope of the methods developed.