Nirmatrelvir, the active ingredient of the Pfizer drug Paxlovid (Figure 1), is an inhibitor of the SARS-CoV-2 main protease enzyme.1 A key transformation- the final synthetic step in the synthesis of Nirmatrelvir- is dehydration of a primary amide (Figure 2).The amide starting material is prepared by reaction of the corresponding ester with ammonia.2 Various methods

The use of fluorine and fluorine-containing functional groups in medicinal chemistry, agrochemicals and advanced materials has grown over the past fifty years.1 Not surprisingly this increase in utility tracks with notable developments and refinements in safe and accessible synthetic methodology, both on the discovery and development front and in subsequent manufacturing. A recent example that caught

At the Scientific Update OPRD conference in Milan earlier this month, Xiaohu Deng from Kura Oncology discussed a pyrimidine-derived diazo intermediate that exists predominantly in the tautomeric ‘tetrazole’ form at equilibrium in solution.[1] The compound was shown as a putative retrosynthetic building block for synthesis of a J&J P2X7 antagonist (Figure 1).[2] I’d not come

                    The naturally occurring cinchona alkaloids, and Quinine in particular, have been of interest to synthetic chemistry practitioners for many years, due ostensibly to its antimalarial activity, particularly against resistant strains of the disease. The original synthesis, by Woodward and Doering in 1944 was heralded as

         2-Aminopyrides are useful synthetic intermediates and pharmacophores in a number of drugs.[1] The Chichibabin reaction, developed in the 1900’s gives a direct method for the amination of pyridine and pyridine derivatives (azines and azoles) using sodium or potassium amides. Intramolecular amination reactions are also known. The reaction can be run either

I always look forward to publication of the annual review synthetic approaches to the new drugs approved for the preceding year. In some ways its bitter sweet since it acts as a reminder of how difficult drug discovery and development is and how the large volume of molecules that start their journey never actually make