Continuous-Flow Synthesis of the Nucleobase Unit of Remdesivir

The Chen group at Fudan University have hit the ground running in 2022, having already published two articles and a review paper involving the Coflore ACR.

In one of the papers, titled “Continuous-flow synthesis of the nucleobase unit of remdesivir”, the group successfully employed the Coflore ACR to facilitate the flow processing of slurries in the N-amination of pyrrole-2-carbonitrile. This reaction, shown in figure 1 below, involved addition of suspensions of NaH and Ph2PO(O)NH2 in THF to pyrrole-2-carbonitrile and precipitation of solid by-products.

Reaction scheme for the N-amination of pyrrole-2-carbonitrile
Figure 1: N-amination of pyrrole-2-carbonitrile

Whilst this reaction was found to take 5 h under batch conditions, the group were able to achieve 97% yield with just a 6-minute residence time! The Chen group stated “Moreover, continuous processing was easily maintained through the ACR for a period of over 10 h. Hence, it was demonstrated that the continuous-flow processing of slurries could be successfully performed using the ACR.”

Overall, the Chen group were able to successfully develop a five-step fully continuous-flow synthesis of the nucleobase unit of the antiviral drug remdesivir from the widely available and inexpensive starting material pyrrole. You can access the paper (open access) in the link below:

The other papers are titled “Development of a Fully Continuous-Flow Approach Towards Asymmetric Total Synthesis of Tetrahydroprotoberberine Natural Alkaloids” and “Continuous flow technology-a tool for safer oxidation chemistry” respectively and are listed on the publications section of our website, linked below:

The team at AM Technology are always interested to learn about the research performed with our Coflore systems. If you have presented or published work with an ACR, ATR or RTR then please feel free to let us know at

“One of today's most important tools for modernizing the pharmaceutical industry is a process known as continuous manufacturing”

Director of the FDA’s Center for Drug Evaluation and Research, Janet Woodcock M.D.