Medicinal chemist Cara Brocklehurst was inspired by her grandfather

6 Sep 2013

What does your current job involve?
I've been at Novartis for eight years, after originally coming to Basel, Switzerland for a postdoc. I currently manage a team of two within Novartis Research (NIBR) in the Global Discovery Chemistry Prep Labs. My group is one of six labs with the task of scaling up medicinal chemistry protocols to provide key intermediates, building blocks and drug candidates for screening purposes. We generally work in the range of 50-200g; which is not enormous but can bring its challenges.

As we are scaling up the protocols for the first time, we frequently have to troubleshoot so the procedures are amenable to larger scale. Sometimes, we perform quick-route scouting to find alternatives or prepare the starting materials ourselves. Often faced with reactions that are challenging to scale because they utilise hazardous reagents, or the materials involved show large exothermic decomposition, we have been looking for new technologies that can help. For the past five years, we've been investigating whether flow chemistry can help us to safely scale up challenging reactions in a continuous manner.

You presented at the 2nd SCI/RSC Symposium on Continuous Processing and Flow Chemistry in September 2013
The symposium gave a great overview of how flow chemistry can be applied to many different chemistries, the impact in the chemical industry and, in particular, the drug discovery process. I presented the NIBR Prep Labs' strategy in scaling up hazardous reactions in flow and I illustrated the talk with real practical examples from our group. Rather than building equipment ourselves, we use commercially available machines, which suit our needs well. We have taken a very pragmatic approach to adapting flow to our needs so I hope the examples are easy for others to go away and try.

What are the advantages of flow production over batch production?
From the perspective of our scale-up group, the main benefit of flow chemistry is that we can perform previously forbidden chemistries in a safe manner. We can prepare potentially dangerous intermediates in situ and we can avoid working with large reaction volumes with the potential to run away.

We have a few examples in which improved selectivities were observed but, despite being most welcome, this is not reliably the case. In the last few years, we have scaled up batches of intermediates that are building blocks for drug candidates going further into development. We have been able to transfer some protocols through to the process research chemists thus saving valuable time.

What made you decide to pursue a career in science?
Inspired by my grandfather, I wanted to be a scientist before I even understood what it really entailed. I love the practical side of chemistry and will never tire of running reactions. Sadly, as the years go by, I become more and more office-bound with less time to potter in the lab. I really enjoy my current position because I get to see, and hopefully influence, how molecules progress through research, yet still have a lot of contact with the real chemistry and the practical side of the science.

What are the most important things you've learned in your career so far?
You need to be an optimist to work as an organic chemist because the really good reactions only work after much perseverance. I wish I'd listened more in my German classes at school because only now do I realise how important it is and how very much harder it is to learn a language when you are older. Every now and again, partake in shameless publicity on behalf of your team because others won't necessarily see the wonderful work you're doing unless you tell them about it.

If you hadn't pursued a career in science, what would you be doing now?
I am a big fan of crafts and so I suppose I would have been working as a potter or doing something with my hands. I recently did a pottery course and was inspired by the wonder of glazing. The colours of the metals only come to life after firing and you never know what you will see when you open the kiln.

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