Synthesis of Danuglipron: Design and Development of a Robust Telescoped C–O Coupling─Deprotection Sequence

Organic Process Research & Development 2026

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Authors: 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
+13 more 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
DOI: 10.1021/acs.oprd.6c00006
Cited by: 2
References: 21

Abstract

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.

Fields of Study & Subjects

Marine Toxins and Detection Methods Synthetic Organic Chemistry Methods Pharmacological Receptor Mechanisms and Effects

Publication details

Journal / source
Organic Process Research & Development
Publisher
American Chemical Society (ACS)
Volume
30
Issue
4
Pages
974–985
Publication date
16 March 2026
Language
EN