One-Pot Reductive Alkylation of 2,4-Dihydroxy Quinolines and Pyridines.

A one-pot, Hantzsch ester-mediated Knoevenagel condensation-reduction reaction has been developed for alkylation of a wide range of substituted 2,4-quinoline diols and 2,4-pyridine diols with aldehydes. The process is operationally simple to perform, scalable, and provides highly useful C-3 alkylated quinoline and pyridine diols in yields of 58-92%. The alkylation products can be converted to 2,4-dihaloquinoline and pyridine substrates for further functionalization.

Sustainable Practices in Medicinal Chemistry Part 2: Green by Design.

With the development of ever-expanding synthetic methodologies, a medicinal chemist's toolkit continues to swell. However, with finite time and resources as well as a growing understanding of our field's environment impact, it is critical to refine what can be made to what should be made. This review seeks to highlight multiple cheminformatic approaches in drug discovery that can influence and triage design and execution impacting the likelihood of rapidly generating high-value molecules in a more sustainable manner. This strategy gives chemists the tools to design and refine vast libraries, stress "druglikeness", and rapidly identify SAR trends. Project success, i.e., identification of a clinical candidate, is then reached faster with fewer molecules with the farther-reaching ramification of using fewer resources and generating less waste, thereby helping "green" our field.