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SELECTBIO Conferences Flow Chemistry Congress 2018

Flow Chemistry Congress 2018 Agenda

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Monday, 12 November 2018


Conference Registration, Materials Pick-Up, Morning Coffee


Ferenc DarvasConference Chair

Welcome from The Chairman of The Flow Chemistry Society
Ferenc Darvas, Chairman, Flow Chemistry Society, Switzerland

Session Title: Conference Opening Session Chaired by Professor Aaron Beeler, Boston University
Session Chair: Aaron Beeler, Assistant Professor, Boston University, United States of America


Aaron BeelerConference Chair

Flow Chemistry Congress 2018 Introduction, Topics and Themes Addressed: The Field of Flow Chemistry, circa 2018
Aaron Beeler, Assistant Professor, Boston University, United States of America


Peter SeebergerKeynote Presentation

Making Affordable Drugs by Continuous Processes
Peter Seeberger, Managing Director, Max Planck Institute of Colloids and Interfaces, Professor Freie Universität Berlin, Germany

The use of flow reactors to screen reaction conditions automatically, to discover more efficient chemical transformations and to produce affordable essential drugs.


Reactions in Flow to Enable Synthesis and Medicinal Chemistry
Aaron Beeler, Assistant Professor, Boston University, United States of America

In the Beeler Research Group, we are developing new technologies and approaches to enable synthesis and medicinal chemistry. The lecture will highlight developments in challenging reactions which can be used to access bioactive small molecules which are critical in our multidisciplinary and collaborative research. A common theme in our lab is the use of flow chemistry to overcome boundaries that limit reactions and to develop efficient reaction processes. Why flow chemistry? Reactions have been carried out in batch vessels for over two centuries and amazingly the tools chemists use have remained largely unchanged. As such, many of the challenges presented by batch reactions are still unsolved. Limitations such as mass transfer, heat transfer, or photon penetration can undermine the potential of a reaction when using traditional batch reactors. However, these limitations are largely mitigated in flow which enables us to reconsider the utility of many transformations for application in synthesis. Ultimately, I hope to demonstrate how flow chemistry provides us a tool for development of new and more efficient reactions that are robust, highly scalable, and provide access to complex and novel chemotypes.


Morning Coffee Break and Networking in the Exhibit Hall


“The When, Why, and How of Flow Chemistry”
Timothy Jamison, Robert R. Taylor Professor and Department Head, Massachusetts Institute of Technology, United States of America

Flow chemistry has the potential to revolutionize the synthesis of organic molecules.  Flow systems can reduce reaction times, increase efficiency, and obviate problems often encountered in scaling up.  In addition to these important practical advantages, flow chemistry expands the “toolbox” of organic reactions available to scientists engaged in the synthesis of molecules – from small-scale experiments to large-scale production.  These benefits are a direct result of several features of flow synthesis that batch synthesis typically cannot achieve, for example, the ability to control fluid flow precisely, the access to temperature and pressure regimes not usually considered to be practical, and the enhanced safety characteristics of flow chemical systems.  In this lecture we will discuss some of our investigations in this area in the form of case studies, wherein a specific target or family of organic molecules has served as an inspiration for the development of new methods of organic synthesis in flow.  Flow chemistry represents an important conceptual advance in the design and execution of chemical syntheses.


Acceleration of Drug Discovery Through the Judicious Application of Enabling Chemistry Technology
Stevan Djuric, Vice President, Discovery Chemistry & Technology and Distinguished Research Fellow, AbbVie, United States of America

The talk will focus on efforts to speed up components of the Drug discovery process that can be influenced by chemistry, namely, cycle time, probability of success and cost of goods.

The following will be highlighted:

  • Flow chemistry platforms for compound library production
  • Fully integrated synthesis-purification- bioassay platforms
  • Flow chemistry at high temperature to access key heterocyclic compounds for FBDD activities
  • Reaction acceleration using microdroplet chemistry


Networking Lunch and Poster Viewing

Session Title: Emerging Technologies and Approaches in Flow Chemistry


Photochemistry as an Enabling and Scalable Tool
François Lévesque, Associate Principal Scientist Process Chemistry, Merck & Co., United States of America

The past ten years have seen the exponential growth of reactions promoted by visible and UV light. This has led to the discovery of very useful and highly selective transformations that were not feasible without the use of photons. Due to the unique advantages of these reactions, we foresee an increasing use of photochemistry chemistry in the synthesis and production of API. Scaling-up these reactions remains a key challenge. As most photochemical reactions require a high surface area to volume ratio for good efficiency, the utilization of these transformations on large scale is most amenable to flow.  Our discussion will highlight the key parameters that need to be taken into account for an effective transition from the lab scale to preparative scale, namely geometry of the reactor, light source, photon density, path length, and residence time. Ongoing efforts by the flow chemistry team at Merck & Co., Inc. toward developing scalable photochemical reactions in flow and their application in specific case studies will be presented.


Tunable Chiroptical Induction Using Synchrotron-Sourced Circularly Polarized Light
Amanda Evans, Scientist, Los Alamos National Laboratory, United States of America

This talk will focus on the use of circularly polarized (cp), or “chiral”, light as a supramolecular chiroptical field for the induction of asymmetry in small molecule building blocks as a continuous photochemical process. A series of batch and continuous photochemical processing experiments have been performed using synchrotron-sourced cp light as the sole source of chiroptical induction under a number of different conditions. A mechanism for asymmetry generation in these small molecule building blocks in solvent and methods for enhancing the initial selectivities observed will be discussed. Predictive approaches for describing the behavior of similar small molecules will also be presented.


The Intersection Between Technology and Need
D. Tyler McQuade, Professor, Virginia Commonwealth University, United States of America

I will present current efforts and success stories related to the Medicines for All Institute (M4All). M4All’s objective is to use advanced chemistry and technology (flow chemistry) to realize low cost manufacturing process for critical medicines.


Afternoon Coffee Break and Networking


Fully Continuous Mulit-Step GMP Synthesis of Drug Substance in a Fume Hood Facility
Joel Calvin, Research Scientist, Eli Lilly and Company, United States of America

Development and implementation of flow process to make drug substance that include a Buchi operation for solvent exchange, Grignard formation using magnesium in a CSTR, a Negishi reaction in a solids handling PFR and a continuous anti-solvent/cooling crystallization of API. The process was run at our manufacturing small volume continuous facility.


New Continuous Flow Synthetic Methods with Highly Reactive Intermediates
Hélène Lebel, Professor, Department of Chemistry, University of Montreal, Canada

Continuous flow technology offers many advantages, including the safe manipulation of highly reactive intermediates.  As such, a number of methods for the preparation and the use of diazo reagents in continuous flow have been described in the literature. Another class of highly reaction intermediates that benefit from continuous flow technology are aliphatic diazonium intermediates. The Lebel group has shown that aliphatic diazoniums can be in-situ generated from an amine and a nitrite reagent in the presence of an acid. The reaction conditions are compatible with a large variety of functional groups. The trapping of aliphatic diazoniums with carboxylates, electron rich aromatics and other nucleophiles afforded various synthetic compounds in high yields.  The optimization details and the scope of this methods will be described in this presentation.


Chemistry in Low Earth Orbit
Kenneth Savin, Sr. Associate Program Scientist, CASIS (Center for the Advancement of Science In Space), United States of America

The opportunity to do chemical research on the International Space Station-National Lab will be presented by CASIS (the Center for the Advancement of Science In Space).  The International Space Station provides a unique environment to perform research that can benefit your own efforts and we shall describe the lab and some of the types of research that has been done on station.  In addition to chemical studies performed on station, we will briefly focus on key chemistries that are incorporated into the Space Station Systems.  The hope is that individuals will come away with a new appreciation for the on-station environment and consider developing their own research to be performed on the International Space Station.


SyrrisFlow Chemistry Approaches to Nano- and Micro- Particle Synthesis
Andrew Mansfield, Flow Chemistry Leader, Syrris

The widespread adoption of flow chemistry for organic synthesis is well known.  In more recent years, there has been a huge growth in research into materials applications in flow.  This talk will explore different reactions in nano- and microparticle synthesis with a look into the different approaches that can be used depending on what type of particle is being produced.  It is also important to explore the relevant application areas for the materials research from metal nanoparticles, quantum dots through to drug delivery systems using API encapsulates polymer micro particles.


Vapourtec, Ltd.Research Towards Automated Continuous Flow Peptide Synthesis
Duncan Guthrie, Director & Owner, Vapourtec, Ltd.

Today, the focus of therapeutic pharmaceuticals is beginning to shift away from small molecular medicines and towards larger, peptide based treatments. Peptides have enormous potential as medicinal compounds. They are highly specific and often potent. Solid phase approaches to peptide synthesis are attractive, however challenges remain.  This presentation describes the key achievements in Vapourtec’s work towards gaining benefit from continuous flow approaches to solid phase peptide synthesis.


Huw M. L. DaviesKeynote Presentation

C-H Functionalization Chemistry in Flow
Huw M. L. Davies, Asa Griggs Candler Professor of Chemistry, Emory University, United States of America


Close of Day 1 of the Conference.

Tuesday, 13 November 2018


Morning Coffee and Networking in the Exhibit Hall


Photoredox Catalysis in Flow
Corey Stephenson, Professor of Chemistry, Willard Henry Dow Laboratory, University of Michigan, United States of America

New advances will be presented from our laboratory on photoredox catalysis in flow and the development of a droplet nanofluidics platform for reaction discovery and development.


Opportunities and Challenges for Continuous Flow in Medicinal Chemistry
Peter Morse, Senior Scientist, Pfizer, United States of America

Continuous flow can be a valuable tool for helping to advance medicinal chemistry projects, especially for the rapid scale-up of promising targets. The pace of projects also dictates that solutions be identified and implemented quickly. This talk will cover examples of flow projects done in support of medicinal chemistry at Pfizer, discussing the benefits and challenges associated with working in this space.


LED Irradiation as a Scalable Solution for Flow Photochemistry
C. Oliver Kappe, Professor and Scientific Director, Center for Continuous Flow Synthesis and Processing, University of Graz, Austria

In this lecture, contributions from our research group in the field of continuous flow photochemistry will be highlighted. Emphasis will be given to directly scalable processes performed in plate-based flow photoreactors of different dimensions (internal volumes) using visible light. The core of these reactors consist of one or more glass-chips with an internal mixing structure for enhanced mass transfer, surrounded by LED panels positioned either side of the chip. Such systems allow accurate temperature control using circulation of thermostated fluids of both the reactor channel and LED panel. The translation from lab-scale to pilot and production scale reactors will be discussed.


Photochemical Processes in Flow
Shawn Collins, Full Professor, Université de Montréal, Canada

The development of both new UV- and visible-light mediated processes for photochemical synthesis or photocatalysis will be presented. Of particular focus will be incorporating photochemical flow processes in multi-step flow sequences for the synthesis of high value products.


Recycling Strategies in Continuous Flow
Stephen Newman, Assistant Professor, University of Ottawa, Canada

The continuous nature of flow chemistry makes it ideally suited for recovery and recycling of waste products. Most efforts in this area have focused on improving turnover numbers in catalytic reaction. In this seminar, the automatic recycling of other high value materials will be discussed, enabling stoichiometric reagents to become pseudocatalytic.


Morning Coffee Break and Networking


The Evolution of Material Function Through Continuous-Flow Chemistry
Frank Leibfarth, Assistant Professor, Chemistry Department, University of North Carolina at Chapel Hill, United States of America

Current high-throughput technology for the synthesis and analysis of synthetic copolymers requires complex and cost-intensive infrastructure and is not amenable to lab-scale discovery efforts. We envision a benchtop instrument that rapidly synthesizes, formulates, and analyzes synthetic copolymers powered by a user-friendly graphical interface. This lecture will detail our current efforts toward understanding the fundamental thermodynamic, kinetic, and fluid transport phenomena that influence copolymer structure and composition during continuous-flow macromolecular synthesis. With these parameters quantitatively defined, our efforts towards the systems engineering of high-throughput copolymer synthetic infrastructure will be described.


One Process from Milligrams to Kilograms; Efficient Drug Substance Development Enabled by Continuous Manufacturing Technology
Eric Fang, Chief Scientific Officer, Snapdragon Chemistry, Inc., United States of America

The nature of continuous manufacturing creates new opportunities for efficient and single-cycle process development.  The use of automated, well characterized lab reactors with tight control over process parameters and rich data collection are enabling new ideas in chemical process development.   Lab reactors designed to accurately model production reactors facilitate efficient development of continuous manufacturing processes.  Examples of this scale-by-design process development will be presented, with particular emphasis on reaction types for which flow technology is truly enabling.


Networking Lunch and Poster Viewing


Increasing Global Access to Health Care Through Process Intensification
Frank Gupton, Floyd D. Gottwald Chaired Professor, Virginia Commonwealth University, United States of America

Access to global public healthcare is impacted by many technical, economic, and social factors. It is widely recognized that the resources required to deliver and improve global public health are currently constrained.  A powerful way to increase access is to lower the cost of products and services that have already proven to be effective.  Currently, the cost of producing a wide range of pharmaceutical products is higher than it needs to be. The mission of Medicines for All (M4All) is to transform active pharmaceutical ingredient (API) processes in order to reduce medication cost and improve patient access.  To fulfill this objective, M4ALL has developed a set of core principles for API process development, which are derived from fundamental elements of process intensification that are commonly known but often neglected. These principles have been applied to several global health drugs yielding dramatic improvements in chemical efficiency. The development of novel heterogeneous cross- coupling that support this effort will also be presented.


Sampling and Analyzing in Flow (PS, Solids are No Longer a Problem)
Michael Organ, Professor and Director of the Centre for Catalysis Research and Innovation , University of Ottawa, Canada

In-process reaction monitoring with GCMS, LCMS, and NMR spectroscopy has been developed to accurately track reaction performance. This has facilitated the incorporation of feed-back loops between the reactor effluent stream and the front end of the reactor using in-house developed software for hands-free continuous reaction optimization and production monitoring. Of course, samples must first be extracted from continuous processes in order to perform the above mentioned in-line analysis. This is often times thwarted by the presence of solids in the flowing stream, which can both block lines and valves and make analyses inaccurate. We have developed technology for the reliable handling of samples that contain solids from flow streams. This will be discussed in the lecture.


Afternoon Coffee Break and Networking


Application of Flow Chemistry Under MedChem Setting
Ping Zhang, Research Investigator, Novartis Institute of Biomedical Research, United States of America

In early drug discovery stage, the key challenges are how to access the desired compounds as fast as possible and how to achieve rapid scale of up the hits. The benefits brought by flow chemistry provide us unique opportunities to tackle both problems. In this presentation, I will be sharing a few stories on how do we use flow technologies to solve problems under medchem settings.


Towards an Integrated Continuous Flow Synthesis of Lumefantrine
Luphumlo Ncanywa, Researcher, Paul Watts Laboratory, Nelson Mandela Univerisity, South Africa

The overall aim of this research project is to develop and optimize synthetic process of Lumefantrine in continuous processing.  This will provide a step change in pharmaceutical manufacturing technology that will increase the availability and affordability of antimalarial drugs such as Lumefantrine.


Close of Day 2 of the Conference.

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