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This work describes a synthesis method for danuglipron, aimed at efficient production for diabetes and obesity treatment.
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.
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Afrin et al. (2026) studied this question.
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