8:00-8:30 Coffee

Integration of Synthesis and Purification

8:30-8:40 Chairperson's remarks
Dr. Daniel B. Kassel, Senior Director, Drug Discovery, Syrrx, Inc.

8:40-9:10 Walk-Up (Mass-Directed) Purification for the Medicinal Chemistry Laboratory- A Key Technology to Support Lead Generation, Lead Optimization and Everything in Between
Dr. Daniel B. Kassel, Senior Director, Drug Discovery, Syrrx, Inc.
The combichem revolution of the late '90s challenged the analytical chemistry community to develop automated, high throughput purification technology to support large synthetic libraries. Now, the focus of most medicinal chemistry groups has shifted to "focused library synthesis" and fast "one-off" synthesis. Independent of the size, scale or stage of synthesis, the key analytical challenge has been to streamline the purification process, initiating with synthesis and culiminating in compound registration. This presentation will provide a brief history and a forward looking view of the technique of mass directed purification .

Keynote Lecture 9:10-9:50 Fluorous Techniques for Rapid Synthesis and Separation Prof. Dennis Curran, Department of Chemistry, University of Pittsburgh Methods to synthesize both individual compounds and focused libraries need to be fast and convenient, yet still provide products of high purity. Fluorous synthesis techniques meet these conflicting demands by allowing for solution phase synthesis with rapid yet substantive separations over silica gel with a fluorocarbon bonded phase. An overview of the use of fluorous reagents, scavengers, and substrates will be presented with an emphasis on techniques suitable for rapid parallel or serial synthesis.

9:50-10:20 Recent Developments in Polymer-Supported Reagents, Catalysts and Scavengers
Dr. Philip Hodge, Department of Chemistry The University of Manchester
Polymer-supported reagents, catalysts and scavengers (PS-RCS's) allow synthetic reactions to be carried out with the organic reactant in solution, where progress is easily monitored. The main differences between reactions using PS-RCS's and the corresponding soluble reactants, viz. diffusion effects, microenvironmental effects and site-site interaction/non-interaction effects, are well known. It is now time to develop the PS-RCS approach further. Ideally these PS reactants should be easier to prepare, be easier to use, have higher loadings, and be longer lasting. Some possible solutions will be presented. Flow systems provide an interesting approach to meeting some of these aims.

10:20-11:00 Networking Coffee Break

11:00-11:30 New Approaches to High Throughput Purification
Dr. Steve Jordan, Director of Technology Development, CombiPure Ltd.
High Throughput Chemistry has come of age and now makes contributions to lead discovery and lead optimization.Much of this chemistry is highly automated and at the very least done in small parallel arrays .The demand for increased weight and purity of the samples in order to get meaningful data has pushed the bottle-neck down stream to purification and analysis.The need for speed and efficiency in purification is now greater than ever. Robust automation and tracking in the purification process has often been the weak link.This talk will describe new systems capable of purifying large numbers of compounds at high speed.

11:30-12:00 New Developments of Bound Reagents and Scavengers for Organic Synthesis and Purification
Dr. Sukanta Bhattacharyya, Argonaut Technologies, Inc.
This presentation will include a technology overview and demonstrate how polymer-supported reagents and solid-phase extraction (SPE) increase efficiency in organic synthesis and purification. Advances in this technology are critical to drug discovery as expedient generation and optimization of new chemical entities is essential. Development of novel polymer-supported reagents for reductive amination, amide formation, oxidation and palladium-catalyzed C-C bond forming cross-coupling reactions will be described. Modular strategies for synthesis and purification applying polymer-supported reagents, SPE and flash chromatography will be discussed.

12:00-1:30 Lunch (on your own)

1:30-2:00 Fluorous Purification Techniques
Dr. Philip E. Yeske, President and CEO, Fluorous Technologies
The application of fluorous chemistry in a medicinal chemistry environment is increasing at a rapid pace. Key to this growth is a suite of simple purification techniques by which fluorous materials can be easily separated from organic materials at a variety of scales. This talk will provide an overview of those techniques along with supporting application data to aid the interested end-user.

2:00-2:30 Implementation of Modern Chromatographic Techniques for High-Throughput Purification
Mr. William Farrell, Senior Scientist, Discovery Technologies, Pfizer Global R&D
The analysis and purification of combinatorial libraries is a challenge for any one chromatographic technique and several approaches are necessary to overcome the limitations of a particular technique in order to maintain a high throughput process.The implementation of traditional UV-based HPLC, mass-triggered HPLC and SFC purification techniques into a single process will be presented.

2:30-3:00 High-Throughput Purification in Support of Early Drug Discovery
Dr. Wolfgang Goetzinger, Director, Analytical Chemistry, ArQule, Inc.
The emergence of automated synthetic platforms has provided the opportunity to synthesize thousands of individual and spatially addressable compounds per year on a routine basis. The availability of large numbers of diverse and pure compounds from parallel synthesis approaches is considered a key element in current drug discovery strategies. Since most synthetic reactions do not yield high purity compounds without workups like liquid-liquid extraction, solid phase extraction or chromatography, high throughput post-synthetic workups are becoming an integral part of any high throughput parallel synthesis strategy. We will discuss how different approaches can be designed to address the specific needs at different points in the development process. All approaches are based on RP-HPLC as a separation technique combined with analog or MS based fraction triggers. Commercially available software tools support the fractionation and the fraction tracking is based on in-house software. The sets of modular purification tools we will present are aimed at putting the emphasis on resolution, speed or recovery and therefore enable the researcher to achieve the desired outcome. The high throughput core technology is therefore useful for purification in support of hit generation as well as lead optimization and we will discuss the impact of this technology on the discovery process.

3:00-3:30 Process Technologies for Purity Enhancement of Large Discovery Libraries
Dr. Mark R. Player, Senior Director, Chemistry, 3-Dimensional Pharmaceuticals Inc.
We have developed production and post-production process technologies for the purity enhancement of large (>10,000-member) discovery libraries. During solid-phase synthesis using the IRORI system, monomer and scaffold rehearsal can select for poorly performing monomers that contain moieties which, at first glance, appear to be nonoffensive to the synthetic approach in question. In addition, high-throughput LCMS with ELS detection with subsequent forensic examination of the side products is used to enable monomer structure-purity relationships to be defined that allow modified monomer selections which maintain diversity, yet result in enhanced purity during the production phase. Exemplifications of this approach using several solid-phase libraries will be presented.

3:30-4:00 Networking Refreshment Break and Dessert

4:00-4:30 Integrating High-Throughput Synthesis and Purification to Efficiently Deliver High Quality Compounds for Discovery
Dr. David Houck, Director, Analytical Sciences, Scynexis, Inc.
We will present the challenges and solutions of integrating parallel synthesis with the purification and analytical QC processes of discovery-library production. This presentation will focus on the key technical issues that every discovery operation must tackle to ensure that quality chemistry is efficiently delivered for biological evaluation: compound design, production, recovery, purity, identity, and distribution. Several real chemistry examples will be provided to illustrate the process and techniques.

4:30-5:00 The Use of SFC to Advance Library Design and Streamline Organic Synthesis
Dr. Terry Berger, Chief Technical Officer, Mettler-Toledo AutoChem, Inc.

5:00-5:30 Panel Discussion

5:30 Close of Conference