Staffan Karlsson*, Helen Benson, Calum Cook, Gordon Currie, Jerome Dubiez, Hans Emtenäs, Janet Hawkins, Rebecca Meadows, Peter D. Smith, Jeffrey Varnes
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引用次数: 3
Abstract
With the first generation medicinal chemistry synthesis as a starting point, we describe herein process development of AZD4573, an oncology drug candidate. In addition to improved yields and removal of chromatographic steps, we have addressed other factors such as availability of starting materials as well as safety of the chemistry involved. With several steps involving volatile, reactive, and non-UV active materials, reaction optimization was facilitated by implementing off-line 1H NMR analysis of crude mixtures. Key transformations targeted for process development included a Wolff–Kishner reduction, an iridium-catalyzed borylation, and enzymatic resolution of a racemic amino-ester.
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.