Process Development and Large-Scale Synthesis of MK-6186, a Non-Nucleoside Reverse Transcriptase Inhibitor for the Treatment of HIV

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2012-01-24 DOI:10.1021/op200334x

Adrian Goodyear*, Xin Linghu*, Brian Bishop, Cheng Chen, Ed Cleator, Mark McLaughlin, Faye J. Sheen, Gavin W. Stewart, Yingju Xu, Jingjun Yin.

引用次数: 6

Abstract

A new synthetic route has been developed to drug candidate 1, a second-generation NNRTI being developed as a potential treatment of HIV. Regiocontrol in a key alkylation step was achieved by selective N-alkylation of hydrazone 13. After a deprotection and cyclisation sequence, 1 was isolated in six steps in 35% overall yield from readily available starting materials.

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用于治疗HIV的非核苷类逆转录酶抑制剂MK-6186的工艺开发和大规模合成

一种新的合成途径已经发展到候选药物1，第二代NNRTI正在开发作为HIV的潜在治疗方法。通过对腙13的选择性n -烷基化，实现了关键烷基化步骤的区域控制。在脱保护和循环序列后，1从现成的起始材料中以35%的总收率分六步分离出来。

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.