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在恩昔瑞韦关键中间体α,α-二取代1,3,5-三嗪的制备中，小改变带来大改进。

Small change for big improvement in the preparation of the key intermediate , -disubstituted 1,3,5-triazone of ensitrelvir.

作者信息

Hu Wei, Liu Yuanchang, Zhang Xiang, Zheng Panpan, Yang Feifei, Guo Guangyang, Xie Xin, Huang Jiuzhong, Chen Weiming

机构信息

School of Pharmaceutical Sciences, Gannan Medical University Ganzhou 341000 P. R. China

Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University Ganzhou 341000 P. R. China.

出版信息

RSC Adv. 2023 Jan 25;13(6):3688-3693. doi: 10.1039/d2ra07844a. eCollection 2023 Jan 24.

DOI:10.1039/d2ra07844a
PMID:36756552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9890673/
Abstract

In this study, the key intermediate , -disubstituted 1,3,5-triazone of ensitrelvir fumaric acid, approved in Japan for the treatment of SARS-CoV-2 infection under the emergency regulatory approval system, was produced from -ethylisothiourea hydrobromide and aminomethyl triazole with CDI by four-step telescoped strategy including CDI-activated, condensation, CDI-cyclization, and -alkylation. The strategy with simple conditions and operations had a total yield of 53% on a gram scale. The strategy for synthesizing the key , -disubstituted 1,3,5-triazone intermediate of ensitrelvir might provide a new avenue for further research and development of ensitrelvir analogs.

摘要

在本研究中，富马酸恩昔瑞韦的关键中间体，即1,3,5-三嗪二取代物，在日本紧急监管批准制度下被批准用于治疗SARS-CoV-2感染，它是由氢溴酸-乙基异硫脲和氨基甲基三唑与羰基二咪唑通过四步缩合策略制备而成，包括羰基二咪唑活化、缩合、羰基二咪唑环化和-烷基化。该策略条件和操作简单，克级规模下总收率为53%。合成恩昔瑞韦关键的1,3,5-三嗪二取代中间体的策略可能为恩昔瑞韦类似物的进一步研发提供新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/247685048af3/d2ra07844a-s6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/1de49f275941/d2ra07844a-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/8b017665b482/d2ra07844a-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/4767cbf8c42f/d2ra07844a-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/15efe61db3a6/d2ra07844a-s4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/22dee46b4ac7/d2ra07844a-s5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/247685048af3/d2ra07844a-s6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/1de49f275941/d2ra07844a-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/8b017665b482/d2ra07844a-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/4767cbf8c42f/d2ra07844a-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/15efe61db3a6/d2ra07844a-s4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/22dee46b4ac7/d2ra07844a-s5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/9890673/247685048af3/d2ra07844a-s6.jpg

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