Reiterative Chiral Resolution/Racemization/Recycle (RRR Synthesis) for an Effective and Scalable Process for the Enantioselective Synthesis of a Dual IDO1/TDO2 Inhibitor Imidazoisoindole Derivative

Herein, we report an effective and scalable highly enantioselective synthesis of an 5H-imidazo­[5,1-a]­isoindole derivative via an RRR-synthesis approach (resolution–racemization–recycle). Chiral resolution performed with the aid of 2,3-dibenzoyl-d-tartaric acid allowed the obtaining of the desired enantiomer in high enantiopurity (>99% ee) and good yield. The undesired enantiomer was subjected to racemization under basic conditions and again to resolution, improving the efficiency of the entire process. The asymmetric formation of the new stereocenter in an early stage of the synthesis scheme was also investigated by means of organocatalytic systems.