Synthesis of Danuglipron: Design and Development of a Robust Telescoped C–O Coupling─Deprotection Sequence
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.
Authors
- Unjila Afrin (ORCID: https://orcid.org/0000-0002-1338-5056)
- Angela L. A. Puchlopek-Dermenci
- Taegyo Lee (ORCID: https://orcid.org/0000-0001-7847-8264)
- Yexenia E. Nieves-Quinones
- Aaron F. Baldwin (ORCID: https://orcid.org/0000-0002-5621-0555)
- Adam Scott
- Giselle P. Reyes
- Melissa Lee (ORCID: https://orcid.org/0000-0002-0216-0193)
- Steven J. Fussell
- Steven J. R. Twiddle (ORCID: https://orcid.org/0009-0000-2670-0070)
- Md Kamrul Hasan Khan (ORCID: https://orcid.org/0009-0004-9835-5594)
- Jonathan Fifer
- Sergei Tcyrulnikov
- B. Adam Williams (ORCID: https://orcid.org/0009-0001-1558-9562)
- Gerald A. Weisenburger
- David F. Fernández (ORCID: https://orcid.org/0000-0003-3482-0894)
- Ursula Sheridan
- Andres R. Faria Quintero
- Shanjun Huang
- Nga M. Do
- Rachel Ruest
- Arlene P. Bartolome
- Gary R. Jolin
- Laura McGivern
- Chase Anthony Salazar
Institutions
- University of Wolverhampton (GB)
- Pfizer (United States) (US)
- Pfizer (United Kingdom) (GB)
- Pfizer (Ireland) (IE)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2026-03-16
- DOI
- https://doi.org/10.1021/acs.oprd.6c00006
- Primary Topic
- Marine Toxins and Detection Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00