The design of proteolysis targeting chimeras (PROTACs) has become a promising technology for modifying a protein of interest (POI) through protein degradation. Herein, we describe the synthetic pathway to develop N4-(2-amino-4-fluorophenyl)-N1-(3-{2-[2-(3-{[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-4-yl]amino}propoxy)ethoxy]ethoxy}propyl)terephthalamide, which was designed to work as a selective degrader of histone deacetylase-3 (HDAC3). The newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR and HRMS. The title compound was tested in vitro against human class-I HDACs isoforms and showed IC50 = 3.4 µM against HDAC3; however, it did not show degradation for the targeted HDACs.
