Synthetic organic reactions are a fundamental enabler of small-molecule drug discovery, and the vast majority of medicinal chemists are initially trained--either at universities or within industry--as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead-optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist.
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