An improved synthesis of Lu AA20465

A solution phase synthesis for the preparation of the glycine transporter 1 (GlyT1) inhibitor Lu AA20465 is presented, which relies on the straightforward assembly of the target molecule through a series of innovative reaction steps. The key steps include a regioselective amination reaction, a chemoselective reduction of an aryl nitro group, a diazotization and iodination sequence under nonaqueous conditions and a copper catalyzed thioarylation reaction.