Over the past years the molecules being synthesized for pharmaceutical evaluation have become more complex.  This molecular complexity is designed to increase potency and/or selectivity and improve PK properties.  To synthesize these molecules multi-step synthetic schemes are often required.  The quantity of final product to be generated is small (10-200 mg), and in many cases the reaction conditions have not been optimized.  Many of these compounds contain one or more chiral centers.  The end result is a reaction mixture that may contain the desired product at low levels and require both achiral and chiral purification to generate material with the purities required for biological testing.  In addition the use of automated synthesis equipment increases the number of compounds that are being prepared in a medicinal chemistry laboratory.  For the above reasons purification has become a bottleneck in the medicinal chemistry process.  An efficient analytical and purification process is required to eliminate this bottleneck as well as optimize the overall medicinal chemistry process.<br/> <br/>This talk will discuss recent improvements to the chiral purification process used to support Amgen’s discovery activities.  The goals of these improvements are to reduce purification turnaround times, and increase first pass method development and purification success rates.  Areas to be discussed include analytical method development, high speed purification as well as automation approaches for drying, formatting and characterization of resolved enantiomers.

Process excellence in discovery scale pharmaceutical chiral purifications

253rd National Meeting (2017)

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