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Efficient Large-Scale Process for Tecovirimat via Reactive Distillation for the Preparation of Cycloheptatriene

文献类型：期刊论文

作者Bonku, Emmanuel Mintah3,4; Qin, Hongjian2,3,4; Odilov, Abdullajon3,4; Yang, Feipu4; Xing, Xinglong1; Wang, Xukun1; Guma, Samuel Desta3,4; Shen, Jingshan3,4
刊名ORGANIC PROCESS RESEARCH & DEVELOPMENT
出版日期2023-09-15
页码8
关键词tecovirimat monkeypox cycloheptatriene antiviral drug reactive distillation
ISSN号1083-6160
DOI10.1021/acs.oprd.3c00151
通讯作者Xing, Xinglong(xinglong.xing@vigonvita.cn) ; Shen, Jingshan(shenjingshan@simm.ac.cn)
英文摘要This article describes an effective process for the large-scale synthesis of tecovirimat, an antiviral drug for treating monkeypox. A key intermediate of tecovirimat, cycloheptatriene, was efficiently obtained via a reactive distillation process of 7,7-dichlorobicyclo[4.1.0]heptane to give 82% (91.38% purity by GC) on a 44.8 kg scale. This method avoided the high temperatures (490-520 degrees C) and low yield that detracted from the previous synthesis. After the subsequent Diels-Alder reaction, the process proceeds with one step via the condensation of anhydride and benzohydrazine intermediates to produce the final compound in a 48% overall yield, resulting in a process mass intensity of 28 kg/kg. While many issues related to the previous reported method were avoided, this improved method has been scaled up to a 60 kg batch size with a satisfactory quality of tecovirimat for clinical investigations.
WOS关键词CYCLOADDITION REACTIONS ; 1,3,5-CYCLOHEPTATRIENE ; PYROLYSIS ; COMPLEXES
资助项目Special Foundation of Chinese Academy of Sciences for strategic pilot technology[XDA12050411] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; University of Chinese Academy of Sciences (UCAS)
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001068511300001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/307291]  
专题新药研究国家重点实验室
通讯作者Xing, Xinglong; Shen, Jingshan
作者单位1.Vigonvita Life Sci Co Ltd, Suzhou 215123, Jiangsu, Peoples R China
2.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Key Lab Plant Resources & Chem Arid Reg, Urumqi 830011, Xinjiang, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Bonku, Emmanuel Mintah,Qin, Hongjian,Odilov, Abdullajon,et al. Efficient Large-Scale Process for Tecovirimat via Reactive Distillation for the Preparation of Cycloheptatriene[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2023:8.
APA Bonku, Emmanuel Mintah.,Qin, Hongjian.,Odilov, Abdullajon.,Yang, Feipu.,Xing, Xinglong.,...&Shen, Jingshan.(2023).Efficient Large-Scale Process for Tecovirimat via Reactive Distillation for the Preparation of Cycloheptatriene.ORGANIC PROCESS RESEARCH & DEVELOPMENT,8.
MLA Bonku, Emmanuel Mintah,et al."Efficient Large-Scale Process for Tecovirimat via Reactive Distillation for the Preparation of Cycloheptatriene".ORGANIC PROCESS RESEARCH & DEVELOPMENT (2023):8.

入库方式： OAI收割

来源：上海药物研究所

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