Synthesis of the 3H-labelled 5-HT3 antagonist (RS-25259-197) at high specific activity

Article abstract of DOI:10.1002/(SICI)1099-1344(199605)38:5<425::AID-JLCR860>3.0.CO;2-B

The preparation of the title compound, a selective 5-HT₃ antagonist with anti-emetic properties, is described. The key intermediate involved is 6-bromo-1,2-dihydronaphthoid acid (5), which was synthesized from 4-bromophenylacetic acid by Micheal addition, acid-induced ring cyclization, reduction and dehydration. Compound (5) was selected because it has two labelling sites to ensure high specific activity of the final product. Reduction of amide 6 with carrier-free tritium gas, followed by reduction of the amide functional group with BF₃-OEt₂ and intramolecular cyclization furnished the title compound having a specific activity of 70.4 Ci/mmol and >99% purity.