Development and Optimization of a Scalable Palladium-Catalyzed C–N Coupling and Acid-Catalyzed Protecting Group Removal Telescope Process for the Synthesis of CDK2-Selective Candidate Tegtociclib (PF-07104091)

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-10-09 DOI:10.1021/acs.oprd.5c00269

Tyler Potter, Thomas A. Brandt, Robert David Bright, Yiqing Feng, Michael Herr, Gary R. Jolin, Sarah Karasik, Melissa Lee, Sebastien Monfette, Asaad Nematalla, Robert C. North, Mark A. Olivier, Dylan Pedro, Angela L. A. Puchlopek-Dermenci, Sergei Tcyrulnikov

引用次数: 0

Abstract

PF-07104091 is a cyclin-dependent kinase 2 (CDK2)-selective inhibitor under investigation as an oncology treatment with breast cancer as the leading indication. In this report, we detail the process development and optimization of a telescoped palladium-catalyzed C–N coupling and acid-catalyzed protecting group removal. This optimized process was demonstrated on pilot plant scale production of >700 kg of intermediate 6.

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可扩展钯催化C-N偶联和酸催化去除保护基望远镜工艺的开发与优化

PF-07104091是一种细胞周期蛋白依赖性激酶2 （CDK2）选择性抑制剂，正在研究作为一种以乳腺癌为主要适应症的肿瘤治疗药物。在本报告中，我们详细介绍了伸缩钯催化C-N偶联和酸催化去除保护基团的工艺开发和优化。该优化工艺已在中试工厂规模生产了700公斤中间体6。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

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.