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

By Rana, Abhilash; Mahajan, Bhushan; Ghosh, Subhash; Srihari, Pabbaraja; Singh, Ajay K.

Published on

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.

Journal

Reaction Chemistry & Engineering. Volume 5, 2020, 2109-2114

DOI

10.1039/D0RE00323A

Type of publication

Peer-reviewed journal

Affiliations

  • CSIR

Article Classification

Research Article

Classification Areas

  • API

Tags