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Introduction

This presentation will provide a comprehensive overview of the synthetic strategy and process development for the key secondary amide intermediate in the synthesis of bersacapavir. First, two synthetic routes will be presented, both relying on the reactivity of a trichloromethylketone: a classical method utilizing the haloform reaction to produce the desired carboxylic acid followed by amide bond formation, and an innovative approach that enables direct coupling of electron-poor aniline with trichloromethylketone, achieving high yield and purity with economical starting materials. Special focus will then be placed on developing a catalytic version of the extended haloform-type amidation using 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Optimization through solubility studies led to significant improvements in yield and process mass intensity (PMI) compared to prior methods that utilized 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Finally, we will discuss the advantages derived from put-and-take operations over continuous volume distillation, enhancing the separation and disposal of CHCl₃. Through the refinement of workup conditions and crystallization processes, the reaction yield was improved, and waste treatment was facilitated, resulting in a robust process successfully scaled up across multiple production campaigns.

Speakers

• Dr Florian Medina Johnson & Johnson Innovative Medicine, Belgium

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Venue

United Kingdom

Contact information

Alan Steven
Contact us by email

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