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

✍ Scribed by Leyi Gong; Howard Parnes

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 415 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199605)38:5<425::aid-jlcr860>3.0.co;2-b

✦ Synopsis

The preparation of the title compound, a selective 5-HT, antagonist with anti-emetic properties, is described. The key intermediate involved is 6-bromo-1,2-dihydronaphthoic acid (s), 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 BF,-OEt, and intramolecular cyclization furnished the title compound having a specific activity of 70.4 Ci/mmol and >99% purity.