Manufacturing Process Development for Belzutifan, Part 1: A Concise Synthesis of the Indanone Starting Material
Feng Peng, Lushi Tan, Lu Chen, Stephen M. Dalby, Daniel A. DiRocco, Jianjun Duan, Minyi Feng, Guan Gong, Haiheng Guo, J. Caleb Hethcox, Lu Jin, Heather C. Johnson, Jungchul Kim, Diane N. Le, Yipeng Lin, Wenjun Liu, Jun Shen, Yimei Wan, Chengqian Xiao, Bangping Xiang, Xiang Qun, Jing Xu, Luliang Yan, Weiyi Yang, YE Hong-lin, Yanpei Yu, Jun Zhang
Abstract
A four-step synthesis of the indanone core of belzutifan (MK-6482) is described. This route starts from the commodity raw material dihydrocoumarin and was successfully demonstrated on a large scale to produce indanone 11 in the synthesis of belzutifan, an FDA-approved first-in-class therapy for the treatment of patients with certain types of Von Hippel–Lindau disease-associated tumors.
Topics & Concepts
Raw materialManufacturing processCommodityProcess engineeringManufacturing engineeringComputer scienceEngineeringMaterials scienceChemistryBusinessOrganic chemistryComposite materialFinanceSynthetic Organic Chemistry MethodsInnovative Microfluidic and Catalytic Techniques InnovationSynthesis and Catalytic Reactions