Synthetic toolbox: Amidation

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The amide bond is a ubiquitous functionality; occurring in natural products, polymers and pharmaceutical molecules. In publications by Carey et al.[1] and Roughley et al.[2] investigating the most commonly used chemical transformations in industrial Research and Development (R&D) departments (process and medicinal chemistry) at three large pharmaceutical companies, both included amide bond formation as one of the top ten transformations in these fields. It is therefore unsurprising that amide bonds feature in more than 25% of known pharmaceutical molecules. The top selling drug in 2008 atorvastatin (trade name Lipitor®) with sales of $12.4 billion contains a single amide bond. Other important drug molecules that carry an amide bond include penicillin (antibiotic), paracetamol (analgesic) and chloramphenicol (broad-spectrum antibiotic), Figure 1

  1. J. S. Carey, D. Laffan, C. Thomson and M. T. Williams, Analysis of the reactions used for the preparation of drug candidate molecules, Org. Biomol. Chem., 2006, 4, 2337-2347.
  2. S. D. Roughley and A. M. Jordan, The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates, J. Med. Chem., 2011, 54, 3451-3479.