Efficient and Sustainable Synthesis of a Potent and Selective 5-HT7 Receptor Antagonist Using a Mechanochemical Approach

Recently, ball milling has become an excellent tool in synthetic organic chemistry as it offers several advantages over classical batch synthesis. Here, an efficient and sustainable mechanochemical procedure was developed to obtain PZ-1361, a potent and selective 5-HT₇ receptor antagonist, with significant antidepressant properties in rodents. The elaborated protocol limited the use of organic solvents, reduced the excess of the alkylating agent, and enabled to avoid column chromatography purification of intermediates and the final compound.