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Diverse Applications of Flow Technology in Medicinal Chemistry Ghristina M. Thompson, Jennifer L. Treece, Irini Akritopoulou-Zanze, Stevan W. DjuricAbbott Laboratories, 100 Abbott Park Road, Abbott Park, IL Abstract Flow technologies have been applied to many areas of medicinal chemistry. In thisposter, two distinct methodologies have been developed using meso-scale ficflobwwfncfhihndholidogy.The first is a "droplet" based library synthesis method which allows forthe preparation of a theoretically unlimited number of compounds using a singleTeflon loop, and very minimal amounts of solvent. This method exploits ththe owtuhfeaschhnologyss ability to spatially separate library members along the length of a tubebyemploying immiscible solvents as spacers. The second methodology takes0Sadvantage of the inherent closed nature of flow systems to create noxiouschermicals in situ, react them in a desired way, and then quench them in acontinuous process that allows for very little of the noxious chemical to be prresentat any one time. For this purpose isocyanides, reagents notorious feTOrr ttrheeirYnPplleasant smell, were synthesized in one flow instrument, transferred directly viatubing to a second instrument to perform Ugi reactions, and then quenched withoutthe user ever being exposed to their odor Flow machine basics Pros and Cons Flow reactor benefits include: m Cleaner reactions· Precise timing. Quantity of product increased by“flowing" longer vs. using largersingle batch reactions· Reaction reoptimizationunnecessary· Increased safety · Super Heating: High temperature and pressure in theclosed system allows for superheating of solvents whichsimulates microwave conditions . Flow reactor challenges include: · Solubility m· Reagents or products are ofter insoluble · Product precipitation in line causes tube obstruction , Concentration - The volume of the reaction must be at least as large as the volume of the tube used to maintain optimal
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