Youbao Cui, Jiachen Zhang, Shuyu Liu, Zhenhang Zhao, Mengya Shan, Nan Jiang* and Xin Zhai*,
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An Alternate and Efficient Synthetic Process for a Metabolic Dysfunction-Associated Steatohepatitis Drug: Resmetirom
A novel, efficient, and streamlined process was developed for resmetirom, a first-in-class THR-β agonist for the treatment of MASH. The key innovation of this novel process was the ingenious utilization of a “one-pot” reaction, which simultaneously accomplished aromatic cyclization and the hydrolysis of 3-chloro-4-isopropylpyridazine. This breakthrough circumvented steps of amino protection and deprotection, effectively streamlining the synthetic route from eight linear steps to four steps while maintaining mild reaction conditions. Using commercially available raw materials, the optimized process provided a rapid pathway to synthesize multigram quantities of resmetirom with an assay purity of 98.8% and a corrected overall yield of 44.3%.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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