Dr. Crasto’s news on Continuous flow for drug synthesis

As I mentioned in the past week, I will take some time to provide some of Anthony Melvin Crasto’s information of flow approaches to drug discovery and API synthesis — maybe I should rename this CF list of the week – we shall see. It certainly opened my eyes to how much work is going on in pushing flow chemistry to application in drug discovery — and so many of our readers want to keep up with the latest thoughts and trends. Here is this week’s news:

CF for Rufinamide

A report (Org Process Res Dev 2014, ASAP article) out of Jamison’s group at MIT, provides a 3-step synthesis of Rufinamide in 92% overall yield. The process illustrates a continuous and convergent method, moving away from the isolation of a key organic azide intermediates and a Cu coiled-tube reactor for the cycloaddition reaction to the corresponding desired triazole.

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CF of Artemisinin-derived API products

This is a nice example from Peter Seeberger at al (Chem Comm 2014) where the group of German scienttists applied their savvy in a divergent flow approach to several compounds in the Artemisinin family.

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A cartoon of their approach is shown above — rather than get into the specific chemistry on this one, I point you to their work highlighted in Chemistry World for a detailed account – you don’t want to miss it…..wow, I am impressed — particularly because there is no obvious aromatic chromophore in these compounds that we are often used to in pharma — not saying we can’t handle it, just interesting from the level of sophistication with technology and these synthetic transformations.

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CF on Quinolone 5-HT1B antagonists from Astra Zeneca

The following paper (Synlett 2010)from Zizhang Qian, Ian Baxendale and Steven Ley describes a continuous multi-step microreactor synthesis of a potent 5HT1B antagonist developed by AstraZeneca. In the paper, we start to see the application of scavenging reagents, polymer-supported reagents and in-line purification techniques for the release of desired intermediates to continue to the next step or in the case of this compound, pure at the end. This theme will be further emphasized in later posts with some of Ian’s reviews on how to utilize these techniques in a strategic format. Happy Reading!

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