Synthetic Development and Scale-Up of the Aminoindazole Fragment of Lenacapavir

This five-step route to fragment <b>1</b> was developed from the initial “fit-for-purpose” large-scale synthesis to a commercially viable process. Key improvements include an alternative condition to hydroxylamine-<i>O</i>-sulfonic acid-mediated nitrile formation and a significant overhaul of the key Miyaura borylation process.

The culmination of all development efforts improved the final product quality and process safety, resulting in a more efficient and higher-yielding process.