Integrated multi-step continuous flow synthesis of daclatasvir without intermediate purification and solvent exchange
Literature Information
Subhash Ghosh
The rapid transmission of viral diseases can cause massive economic damage and loss of life. The manufacture of most anti-viral drugs is normally carried out using batch synthesis which typically requires long production times (3–15 days) and significant manpower and infrastructure. The fabrication of fully integrated flow-based manufacturing systems offers an alternative approach that can be greener and more economical. In this regard, we have developed a compact manufacturing machine for the synthesis of the antiviral API daclatasvir which is easily reconfigured, has a much-reduced footprint, and enables multi-step synthesis using innovative reaction chemistry and post-synthesis purification equipment. The developed integrated system enabled the ultra-fast production of DCV as its free base (within 28.2 min.) with a throughput of 11.8 g per day (equivalent to 200 doses of Daklinza, 60 mg tablets) in 98% HPLC purity.
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Reaction Chemistry & Engineering is an interdisciplinary journal reporting cutting-edge research focused on enhancing the understanding and efficiency of reactions. Reaction engineering leverages the interface where fundamental molecular chemistry meets chemical engineering and technology. Challenges in chemistry can be overcome by the application of new technologies, while engineers may find improved solutions for process development from the latest developments in reaction chemistry. Reaction Chemistry & Engineering is a unique forum for researchers whose interests span the broad areas of chemical engineering and chemical sciences to come together in solving problems of importance to wider society. All papers should be written to be approachable by readers across the engineering and chemical sciences. Papers that consider multiple scales, from the laboratory up to and including plant scale, are particularly encouraged.
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