Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 1─ Process History and Development Strategy

DA DiRocco, YL Zhong, DN Le… - … Process Research & …, 2024 - ACS Publications
An improved synthesis has been developed for belzutifan, a novel HIF-2α inhibitor for the
treatment of Von Hippel–Lindau (VHL) disease-associated renal cell carcinoma (RCC). The …

Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 6─ Development of a Nucleophilic Aromatic Substitution in Water

DN Le, TJ Wright, E Alwedi… - … Process Research & …, 2024 - ACS Publications
A convergent nucleophilic aromatic substitution (SNAr) was developed as the final step in an
improved manufacturing process to belzutifan. The reaction was performed in water to …

Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 2─ Development of a Scalable Nickel-Catalyzed Sulfonylation

JC Hethcox, J Kim, HC Johnson, Y Ji… - … Process Research & …, 2024 - ACS Publications
A nickel-catalyzed sulfonylation reaction was discovered and developed into a robust
process for the manufacturing of belzutifan, an FDA-approved treatment for Von Hippel …

Enantio-and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation

DN Le, HC Johnson, Y Lam, C Sun, L Cheng… - Organic …, 2024 - ACS Publications
Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed
asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high …