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

• William Connors^a
• Ryan DeKorte^a
• Simon C. C. Lucas^b
• Ariamala Gopalsamy^b
• Robert E Ziegler^a

• ^aAstraZeneca Pharmaceuticals LP, Medicinal Chemistry, United States
• ^bAstraZeneca Pharmaceuticals LP, Hit Discovery, United Kingdom

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.

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