Day Three: Wednesday, February 25

8:30-9:00 Coffee (technology workshop, sponsorship available)

Microwave-Assisted Organic Synthesis

9:00-9:10 Chairperson's remarks
Dr. Oliver Kappe

9:10-9:40 Microwaves in Synthesis: Contributions and Challenges
Dr. Esteban Pombo-Villar, Manager of External Collaborations, Nervous System Research, Novartis Pharma Ltd.
The use of microwave irradiation to deliver energy for organic reactions has increased in popularity in recent times, partially due to the availability of improved instrumentation which allows precise control of reaction conditions such as temperature and pressure. We and others have found that microwave irradiation facilitates numerous chemical transformations, and microwave equipment is becoming a standard tool in the organic chemistry laboratories. In spite of this, there are challenges that need to be met to ensure the impact of this technology can fulfill its current promise. Ongoing work in our laboratories addressing some of these challenges will be discussed.

9:40-10:10 Rapid Scaffold Generation and Decoration Merging Microwave and Combichem Technologies
Dr. C. Oliver Kappe, Associate Professor of Chemistry,Karl-Franzens-University
The use of microwaves for the preparation of diverse dihydropyrimidine libraries will be highlighted, using both solid- and solution-phase technologies. Further decoration of the positions around the heterocylic core utilizing high-speed microwave chemistry in conjunction with the use of polymer-supported catalysts, reagents, and scavengers for synthesis/purification will also be reported. Microwave-assisted scale-up options in both batch and continuous flow mode will be discussed.

10:10-10:55 Coffee Break, Exhibit and Poster Viewing

10:55-11:25 The Utilization of Microwave-Accelerated Synthesis for High-Throughput Lead Optimization
Dr. Daryl R. Sauer Group Leader, High-Throughput Organic Synthesis, Abbott Laboratories
Microwave-Accelerated Synthesis (MAS) has proven to be a highly effective and increasingly popular tool in organic and medicinal chemistry. The use of MAS to accelerate the lead optimization process in pharmaceutical research is a logical and useful extension of this technology. In the High-Throughput Organic Synthesis group at Abbott Labs we have coupled MAS with standardized reaction protocols and automation in an effort to create lead optimization libraries rapidly and efficiently. This presentation will detail reaction protocols and automation platforms that have been developed for this purpose and allowed for the successful implementation of MAS in a centralized parallel synthesis facility.

11:25-11:55 Target Oriented Synthesis of Heterocycles: Microwaves, Parallel Purification, and Design
Assistant Professor R. Kip Guy, Pharmaceutical Chemistry, Director, Bay Area Screening Center; Director, Center for Chemical Diversity, UCSF
Efforts to develop modern, target-oriented methods for the synthesis of libraries of quinolines, acridines, and phenothiazines will be presented. Specific topics will include the use of microwaves in the formation of the heterocycles, the use of scavenger/solid support strategies in the addition of side chains, and the development of high throughput purification strategies.

11:55-12:25 Panel Discussion

12:25-1:25 Luncheon Technology Workshop     
 Sponsored by

How Microwave Technology Can Make a Major Impact in Drug Discovery
Dr. Jon-Sverre Schanche, Biotage
Microwave synthesis offers unprecedented technological advantages for rapid, reproducible and scalable chemistry development. Harnessing and applying these advantages to positively impact drug discovery, however, is the real challenge where consistency of method, safety and reliability are premium benefits. The advantages and limitations of different technical solutions addressing the issues in medicinal chemstry will be reviewed, and the results of the latest technological developments as well as cutting-edge examples of applications will be presented.

Compound Synthesis in Flow Reactors
Exclusive Session Sponsor

1:55-2:05 Chairperson's Remarks
Dr. Paul Watts, University of Hull

2:05-2:35 Micro-Channel Flow Reactors: Beyond Compound Synthesis
Dr. Terry Long, Technology Consultant, Accendo Corporation
For the past ten years numerous efforts have been made to accelerate drug discovery and development through the commercialization of parallel batch reactors. Unfortunately, the acceleration has not achieved the level to meet corporate objectives. The reason batch reactors are theoretically limited and therefore will never offer the accelerations promised. Drug development must look to a better technology which does not have these theoretical barriers. Research into the use of micro channel flow reactor technologies to synthesize small amounts of organic compound has been steadily growing. With these promising initial results, one can envision using micro channel flow for more than the synthesis of new compounds. Perspectives of micro channel flow technologies in both discovery and development environments to increase knowledge and improve experimental strategies will be discussed.

2:35-3:05 Continuous, Integrated Microchemical Systems for Organic Synthesis
Dr. Klavs F. Jensen, Department of Chemical Engineering, Masachusetts Institute of Technology
Microfabrication techniques and scale-up by replication have fueled spectacular advances in the electronics and telecommunications industries, and more recently, in microanalysis chips for chemical and biological applications. The reduction in size and integration of multiple functions has the potential to produce micro scale chemical synthesis systems with capabilities exceeding those of conventional macroscopic counter parts. Synthesis procedures are enhanced by integrating microfluidic components with sensors and actuators. Cases studies illustrate applications, including realization of chemical pathways generally difficult in conventional systems, point-of-use chemical synthesis, and multiphase reactions.

3:05-3:35 Chemistry in Flow - New Flowthrough Reactors for Solid-Phase-Assisted Catalysis
Dr. Andreas Kirschning, Institute for Organic Chemistry, University of Hanover, Germany
The topic of my talk will deal with new flowthrough reactors which contain a monolithic megaporous composite material made of a polymer and glass. The surface of this composite material is loaded with different reagents and catalysts and the whole system is employed for the automated synthesis in solution. In this context particular focus will also be put on techniques for the immobilization of palladium catalysts on solid supports.

3:35-4:20 Refreshment Break, Exhibit and Poster Viewing

4:20-4:50 BuLi-Mediated Coupling Reactions of Arylbromides under In-Situ-Quench Conditions: A New Concept in Organic Synthesis Suitable for Microreactor Technology
Prof. Dr. Hans-Guenther Schmalz, Institute of Organic Chemistry, University of Cologne
Treatment of a aryl- and heteroarylbromides with butyllithium in the presence of electrophiles (such as ketones, nitriles, dimethylsulfate, etc.) opens an efficient access to a broad variety of valuable synthetic intermediates in an operationally very simple fashion and even allows for the synthesis of valuable compounds, difficult to access by the classical stepwise procedure. Moreover, this in-situ-quench protocol is ideally suited for the performance of organolithium chemistry in commercially available (single-step) flow micro-reactor systems.

4:50-5:20 Continuous Chemistry as a New Approach to Accelerating Drug Development
Dr. Thomas Schwalbe, Chief Executive Officer, Cellular Process Chemistry Systems, GmbH
Continuous Chemistry based on microreaction technology benefits from the continuous conduct of reactions in processing systems of minimal internal hold-up. Its application to combinatorial experimentation is substantially improved by the new approach called "Sequential Organic Synthesis". Sequential synthesis offers higher flexibility than parallel synthesizers. Convention methods in a reaction block operate in limited reaction volumes. Sequential synthesis in a continuously running system allows access to variable amounts of target compounds. In addition, even demanding or divergent syntheses can be performed.

5:20 Close of Day