Direct Synthesis of a PDE4 Inhibitor by Using Pd–Cu-Catalyzed C–H/C–Br Coupling of Benzoxazole with a Heteroaryl Bromide

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2016-05-10 DOI:10.1021/acs.oprd.6b00106

Kiichi Kuroda*, Shinjiro Tsuyumine, Tomohiro Kodama

引用次数: 16

Abstract

A short and practical synthetic route of a PDE4 inhibitor (1) was established by using Pd–Cu-catalyzed C–H/C–Br coupling of benzoxazole with a heteroaryl bromide. The combination of Pd(OAc)₂-Cu(OTf)₂-PPh₃ was found to be effective for this key step. Furthermore, telescoping methods were adopted to improve the yield and manufacturing time, and a two-step synthesis of 1 was accomplished in 71% overall yield.

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钯铜催化苯并恶唑与杂芳基溴C-H / C-Br偶联直接合成PDE4抑制剂

通过pd - cu催化苯并恶唑与杂芳基溴的C-H / C-Br偶联，建立了一种短而实用的PDE4抑制剂(1)的合成路线。Pd(OAc)2-Cu(OTf)2-PPh3的组合对于这一关键步骤是有效的。此外，采用伸缩法提高了产率和制造时间，两步合成1的总产率为71%。

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.