Mémoire, partim B: Synthesis of the [[sup] 18[/sup]F]flumazenil sulfonium salt precursor for application in nuclear medicine

Abstract

In this work, we investigated the feasibility of synthesising the [18F]flumazenil sulfonium salt precursor for application in nuclear medicine. The methodology focused on preparing flumazenil and bromazenil as a reference and a sulfonium salt intermediate respectively, along with the construction of a biarylthioether building block for sulfonium salt cyclization. While the synthesis of the biarylthioether building block showed satisfactory overall yield of 86%, reactions to make imidazobenzodiazepines posed challenges, with an overall yield limited to 5-13%, primarily due to purification difficulties. Furthermore, the coupling between the building block and the bromazenil led to unwanted hydrolysis, hindering the formation of the final product. An alternative pathway was attempted but failed to yield results. A recovery strategy via esterification was explored, but purification issues persisted. These results highlight the challenges that need to be addressed for optimisation of this approach and pave the way for promising clinical applications.