Synthesis of Benzothiazinones from Benzoyl Thiocarbamates: Application to Clinical Candidates for Tuberculosis Treatment

Benzothiazinones are a structural motif found in biologically active compounds, such as the clinical candidates BTZ‐043 and Macozinone for the treatment of tuberculosis. We describe a robust, two‐step method to synthesize 2‐amino‐substituted benzothiazinones from benzoyl thiocarbamates, which were p...

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Bibliographic Details
Published inEuropean journal of organic chemistry Vol. 2022; no. 34
Main Authors Connors, William, DeKorte, Ryan, Lucas, Simon C. C., Gopalsamy, Ariamala, Ziegler, Robert E.
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 13.09.2022
Subjects
API
Continuous flow
Isothiocyanate
Substrates
Sulfur heterocycles
Synthetic methods
Tuberculosis
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Summary:Benzothiazinones are a structural motif found in biologically active compounds, such as the clinical candidates BTZ‐043 and Macozinone for the treatment of tuberculosis. We describe a robust, two‐step method to synthesize 2‐amino‐substituted benzothiazinones from benzoyl thiocarbamates, which were prepared in a one‐pot procedure from benzoyl chlorides. The intramolecular cyclization and ethoxy displacement steps were also amenable to adoption in continuous flow as exemplified by select substrates. We report a strategy for the synthesis of amino‐substituted benzothiazinones using an intramolecular cyclization and ethoxy displacement approach. This resulted in a two‐step synthesis of the anti‐tuberculosis clinical candidates BTZ‐043 and Macozinone without the use of toxic carbon disulfide.
Bibliography:W. C. and R. D. contributed equally.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.202200684