Cu-Catalyzed C–N Couplings with Benzilamide Ligands

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-09-03 DOI:10.1021/acs.oprd.5c00257

Ian Hotham, Daniel W. Widlicka, Robert A. Singer*, David J. Bernhardson and Zheng Wang,

引用次数: 0

Abstract

A linker fragment used in the preparation of an oncology candidate is efficiently synthesized via Cu-catalyzed C–N coupling. The original route required a Cu-catalyzed coupling, followed by an oxidation and protection sequence. After the evaluation of hydroxypicolinamide ligands and other amide ligands as inefficient for a more desirable C–N coupling sequence, screening of new ligands commenced. With a new catalyst derived from Cu salts and dimethoxyphenylbenzilamide (DMPB), the linker fragment can be directly prepared with commodity chemicals, avoiding oxidation. The DMPB ligand for the Cu catalyst is readily prepared from benzilic acid and 2,6-dimethoxyaniline. A brief survey of the scope of this Cu-DMPB system is explored for secondary and primary amines.

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cu催化的苯甲酰胺配体的C-N偶联

通过cu催化的C-N偶联有效地合成了用于制备肿瘤候选物的连接子片段。原来的路线需要一个铜催化偶联，其次是氧化和保护序列。在评价羟基喹啉酰胺配体和其他酰胺配体对于更理想的C-N偶联序列效率低下后，开始筛选新的配体。利用铜盐和二甲氧基苯基苄基酰胺（DMPB）衍生的新型催化剂，可以直接用商品化学品制备连接片段，避免氧化。铜催化剂的DMPB配体是由苯甲酸和2,6-二甲氧基苯胺制备的。简要介绍了Cu-DMPB体系对仲胺和伯胺的适用范围。

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.