一种高效合成ivacator的方法

IF 2 3区化学 Q2 CHEMISTRY, ORGANIC

Journal of Heterocyclic Chemistry Pub Date : 2017-06-14 DOI:10.1002/jhet.2931

Rui Zhang, Guanyu Han, Luobin Jiang, Yao Shen, Rui Yang, Yongjun Mao, Hang Wang

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引用次数: 3

摘要

介绍了一种新的、实用的克级合成方法。采用亲电法在芳香环上加成两个t-丁基，三步合成5-氨基-2,4-二-t-丁基苯酚，收率61%，纯度98.1%(高效液相色谱法)。采用二甲基甲酰胺分子内环化法制备了4-氧-1,4-二氢喹啉-3-羧酸，收率为54%。两部分经缩合，收率为71%，纯度为99.1%(高效液相色谱法)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

An Efficient Synthesis of Ivacaftor

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An Efficient Synthesis of Ivacaftor

New and practical synthetic route of ivacaftor is described on a grams scale. An electrophilic addition of two t-butyl groups to the aromatic ring is adopted to prepare 5-amino-2,4-di-t-butylphenol in 61% yield over three steps with 98.1% purity (high-performance liquid chromatography). An intramolecular cyclization of ethyl 3-(2-aminophenyl)-3-oxo-propanoate with dimethylformamide-dynamic mechanical analysis is used to prepare 4-oxo-1,4-dihydroquinoline-3-carboxylic acid in 54% yield over four steps. Ivacaftor is obtained by condensation of the two parts in 71% yield with 99.1% purity (high-performance liquid chromatography).

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来源期刊

Journal of Heterocyclic Chemistry 化学-有机化学

CiteScore

5.20

自引率

4.20%

发文量

177

审稿时长

3.9 months

期刊介绍： The Journal of Heterocyclic Chemistry is interested in publishing research on all aspects of heterocyclic chemistry, especially development and application of efficient synthetic methodologies and strategies for the synthesis of various heterocyclic compounds. In addition, Journal of Heterocyclic Chemistry promotes research in other areas that contribute to heterocyclic synthesis/application, such as synthesis design, reaction techniques, flow chemistry and continuous processing, multiphase catalysis, green chemistry, catalyst immobilization and recycling.