Kidney cancer is one of the 10 most common cancers in 2020 as indicated by the National Cancer Institute (NCI). The most common type of kidney cancer in adults is the Clear Cell Carcinoma (ccRCC), which represents 80% of Renal Cell Cancer (RCC) cases. Most of the ccRCC tumors are characterized by the inactivation of the tumor suppressor von Hippel-Lindau (VHL), an essential component of the cellular oxygen-sensing pathway. VHL is known to be an interesting target for the development of new therapies in RCC. At present, all the available treatments present limitations, such as resistance mechanisms and adverse effects impacting patients’ lives. This justifies the need of developing a more specific and less toxic therapy to target ccRCC. Proteolysis targeting chimera (PROTACs) represents an alternative strategy to overcome the limitations of actual treatments. PROTACs are heterobifunctional molecules composed of a protein of interest (POI) binder, a E3 ubiquitin ligase binder and a linker that connect the two parts. These heterobifunctional molecules exploit the ubiquitin-proteasome system (UPS) in order to degrade targeted proteins. At present, 4 types of E3 ubiquitin ligases have been already recruited by PROTACs: Von Hippel Lindau (VHL), Inhibitor of Apoptosis Proteins (IAPs), Mouse Double Minute 2 homolog (MDM2) and Cereblon (CRBN). The choice of the E3 ligase is tissue-dependent and, so far, there is still no evidence on which E3 ligase might lead to a more efficient target degradation. For this reason, this project aims to explore the synthesis path of LCL- 161, one of the most recent binders for IAPs ligases. Once synthesized, LCL-161 will be modified in order to be linked to a specific POI binder for HIF-2α, an oncogene that is overexpressed in ccRCC. The final IAP-based PROTAC will be eventually tested in vitro to study its efficacy in ccRCC cells that lack VHL ligase. This project represents a first investigation of the synthesis of LCL-161. The synthesized intermediates were characterized by unusual NMR spectra, which turned out to be difficult to understand. One possible explanation is that the pyrrolidine moiety gave flexibility to all the intermediates, resulting in broadened signals. The synthesis of LCL-161 resulted to be very challenging. In this master’s thesis, 4 synthesis steps had been explored and optimized, as well as the synthesis of the Grignard reagent.