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Integrated multi-step continuous flow synthesis of daclatasvir without intermediate purification and solvent exchange

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Abstract

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.

Graphical abstract: Integrated multi-step continuous flow synthesis of daclatasvir without intermediate purification and solvent exchange

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Article information


Submitted
10 Aug 2020
Accepted
09 Sep 2020
First published
09 Sep 2020

React. Chem. Eng., 2020, Advance Article
Article type
Paper

Integrated multi-step continuous flow synthesis of daclatasvir without intermediate purification and solvent exchange

A. Rana, B. Mahajan, S. Ghosh, P. Srihari and A. K. Singh, React. Chem. Eng., 2020, Advance Article , DOI: 10.1039/D0RE00323A

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