PRODUCTION OF ¹¹C-LABELED AMIDES VIA "IN-LOOP" ¹¹C-CARBONYLATION

Area of Science:

• Radiochemistry
• Molecular Imaging
• Organic Synthesis

Background:

• Benzamides are prevalent in bioactive molecules, making them promising scaffolds for developing Positron Emission Tomography (PET) radiotracers.
• Carbon-11 (¹¹C) labeling is crucial for PET imaging due to its short half-life and favorable decay characteristics.

Purpose of the Study:

• To establish an improved and automated synthesis route for producing primary ¹¹C-labeled benzamides.
• To demonstrate the versatility of the method by synthesizing known PET imaging agents.

Main Methods:

• Utilized carbonylative cross-coupling of aryl halides with ¹¹C carbon monoxide.
• Employed electrophilic aroyl dimethylaminopyridinium salts as intermediates.
• Used GE TRACERLab FX automated radiochemistry synthesis modules.

Main Results:

• Successfully synthesized a variety of benzamide-containing compounds, including the KOR antagonist [¹¹C]LY2795050.
• Achieved moderate to excellent radiochemical yields for the synthesized ¹¹C-labeled benzamides.
• Demonstrated a practical and automated approach for ¹¹C-benzamide synthesis.

Conclusions:

• The developed automated method provides a practical means for synthesizing primary ¹¹C-benzamides.
• This methodology sets the stage for future applications in PET tracer development and molecular imaging.
• The versatile tool advances the generation of ¹¹C-labeled compounds for PET imaging, opening new avenues in biological process understanding.