Practical synthesis of 7-bromo-4-chloro-1H-indazol-3-amine: an important intermediate to Lenacapavir

7-Bromo-4-chloro-1H-indazol-3-amine is a heterocyclic fragment used in the synthesis of Lenacapavir, a potent capsid inhibitor for the treatment of HIV-1 infections. In this manuscript, we describe a new approach to synthesizing 7-bromo-4-chloro-1H-indazol-3-amine from inexpensive 2,6-dichlorobenzonitrile. This synthetic method utilizes a two-step sequence including a regioselective bromination and heterocycle formation with hydrazine to give the desired product in an overall isolated yield of 38-45%. The new protocol has been successfully demonstrated on hundred-gram scales without the need of column chromatography purifications. This new synthesis provides a potential economical route to large scale production of this heterocyclic fragment of Lenacapavir.