Synthesis of tritium-labelled BIBN4096, an experimental h-CGRP-antagonist

Synthesis of tritium labelled BIBN 4096 – 1-piperidine-3H-carboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2 H)-quinazolinyl)-, [R-(R*,S*)]-, – a h-CGRP-antagonist for the treatment of migraine is described. Selective tritiation of a heterocyclic aromatic fragment in the presence of aromatic ring in a precursor of BIBN4096 was successfully carried out using the solid state catalytic exchange method. Subsequent completion of the synthesis sequence gave the final [3H]BIBN4096 with a specific activity of >170 Ci/mmol. Copyright © 2006 John Wiley & Sons, Ltd.