Sub-Micromolar Reaction Screening in Flow
Neal Sach, Senior Principal Scientist, Pfizer
As block-buster opportunities dwindle and personalized medicines
prevail there is a strong drive to reduce drug development costs to
ensure medicine discovery remains a viable proposition. One outcome of
this changing landscape is the pressure to identify scalable synthetic
routes at an earlier stage to minimize any delays in the transition from
small scale pre-clinical work, to large scale patient studies.
Chemical
technologies have played a leading role in that goal over the past two
decades with batch reaction screening tools being central to that
progress. In this presentation, a new and novel flow technology will be
detailed that enables miniature scale chemistry optimization
experiments. The technology reduces the scale of each reaction to less
than 0.01mg, enabling the user the ability to screen over 1500
combinations (solvent, base, catalyst, and temperature) automatically in
24 hours using just 15mg of substrate. The presentation will
demonstrate the technology through a model Suzuki coupling in which over
4500 combinations were attempted in 3 days to arrive at a scalable
process suitable for scale up.
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