Unjila Afrin, Aaron F. Baldwin, Arlene P. Bartolome, Nga M. Do, Andres R. Faria Quintero, David F. Fernández, Jonathan Fifer, Steven J. Fussell, Shanjun Huang, Gary R. Jolin, Md Kamrul Hasan Khan, Melissa Lee, Taegyo Lee, Laura McGivern, Giselle P. Reyes, Rachel Ruest, Adam Scott, Ursula Sheridan, Steven J. R. Twiddle, Angela L. A. Puchlopek-Dermenci, Chase Anthony Salazar, Sergei Tcyrulnikov, Gerald A. Weisenburger, B. Adam Williams, Yexenia E. Nieves-Quinones
Danuglipron tromethamine ( 1 ), a glucagon-like peptide-1 receptor (GLP-1R) agonist candidate, was investigated by Pfizer for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Given the anticipated high clinical and commercial demand for danuglipron tromethamine, the development of a robust, efficient, and sustainable manufacturing process was critical. This work describes the optimization and development of a telescoped process for the initial steps of the synthesis, featuring a Pd-catalyzed C–O coupling and an acidic t -butoxycarbamate deprotection. This is the first of two papers describing the commercial route for danuglipron tromethamine.