Matthew V. Joannou, Matthew J. Goldfogel, Eric M. Simmons, Steven R. Wisniewski
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引用次数: 0
Abstract
The development and execution of a nickel-catalyzed borylation/palladium-catalyzed Suzuki telescoped process utilizing the inexpensive NiCl2·6H2O precatalyst for the borylation step are reported. The development of the borylation reaction was guided by a preliminary mechanistic investigation to understand the origin of the dehalogenated side product. The borylation stream was telescoped into a Suzuki coupling to form a bis-heteroaryl bond in the pentacyclic core of afimetoran, an antagonist of toll-like receptors 7/8 (TLR 7/8). The optimization of the Suzuki reaction and kilogram-scale demonstration of the telescoped process showcase the viability of utilizing nickel catalysis in the development of scalable routes to clinical APIs.
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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