A Tetrazine‐Based Synthesis for Accessing Underutilized Aza‐Indole Analogues

Aza‐indole functionalities fill an important role in drug discovery. While indoles are considered privileged scaffolds, aza‐indoles allow for better pharmacological properties and on‐target activities. Synthetic approaches to access aza‐indoles are limited, with pyrazolopyridazines being some of the scarcest aza‐indoles. To provide access to these underutilized cores, a synthetic approach utilizing a reaction cascade between a protected propargylhydrazine and dichlorotetrazine has been developed. In addition, a variety of methods were developed to access each position on the core for late‐stage functionalization. This method offers an expedited synthetic route to a rare aza‐indole scaffold with superior physiochemical properties when compared to indole analogues.