SYNTHESIS OF THE H-3 LABELED 5-HT3 ANTAGONIST (RS-25259-197) AT HIGH SPECIFIC ACTIVITY

The preparation of the title compound, a selective 5-HT3 antagonist wi th anti-emetic properties, is described. The key intermediate involved is 6-bromo-1,2-dihydronaphthoic acid ((5) under bar), which was synth esized from 4-bromophenylacetic acid by Micheal addition, acid-induced ring cyclization, reduction and dehydration. Compound ((5) under bar) was selected because it has two labelling sites to ensure high specif ic activity of the final product. Reduction of amide (6) under bar wit h carrier-free tritium gas, followed by reduction of the amide functio nal group with BF3-OEt(2) and intramolecular cyclization furnished the title compound having a specific activity of 70.4 Ci/mmol and >99% pu rity.