Jeremy D. Mason, Jan M. Spink, Mahesh Pallerla, Zhenhua Wu, Rajeev K. Singh, Aravind B. Pulipaka, Jia Liu, Marvin Marcus Vega, Xu Wang, Michael J. Sofia, Ganapati Reddy Pamulapati
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引用次数: 0
Abstract
A scalable process for manufacturing of the anticoronavirus clinical candidate AB-343 has been developed. The lactam-containing subunit of the molecule was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation. The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P. AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clinical development.
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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