High-throughput synthesis of azide libraries suitable for direct "click" chemistry and in situ screening

A key challenge in current drug discovery is the development of high-throughput (HT) amenable
chemical reactions that allow rapid synthesis of diverse chemical libraries of enzyme inhibitors. The
Cu(I)-catalyzed, 1,3-dipolar cycloaddition between an azide and an alkyne, better known as “click
chemistry”, is one such method that has received the most attention in recent years. Despite its
popularity, there is still a lack of robust and efficient chemical strategies that give access to diverse
libraries of azide-containing building blocks (key components in click chemistry). We report herein a
highly robust and efficient strategy for high-throughput synthesis of a 325-member azide library. The
method is highlighted by its simplicity and product purity. The utility of the library is demonstrated
with the subsequent “click” synthesis of the corresponding bidentate inhibitors against PTP1B.