Greener synthesis of a potent proteolysis targeting chimera (PROTAC) degrader of indoleamine-2, 3-dioxygenase 1 (hDOI1)<sup></sup>

The synthesis of the potential indoleamine-2, 3-dioxygenase 1 (IDO1) degrader proteolysis-targeting chimeras (PROTAC) using sustainable reagents and technologies such as ionic liquids and photochemical couplings was investigated. The ligand to the protein of interest, an indole derivative, was synthesized successfully for three substrates bearing different substituents (NO2, (CF3)2 and H) over three steps with good to satisfactory results with overall yields ranging from 21 to 71%. However, the coupling with the ubiquitin ligase, pomalidomide, was unsuccessful due to the degradation of the reactive diazoketone functional group.