Synthesis of [11C]celecoxib: A potential PET probe for imaging COX-2 expression

Abstract

[11C]Labeling of celecoxib, a COX-2 selective inhibitor and prescription drug for arthritis and pain has been achieved. The precursor molecule for the radiolabeling was synthesized from 4-bromoacetophenone in 4 steps with 23% overall yield. Stille reaction of N-[bis-(4-methoxyphenyl) phenylmethyi]-4-[5-(4-tributylstannylphenyl)-3-trifluoromethylpyrazol-1-yl] benzenesulfonamide (5) with methyl iodide in presence of catalytic amounts of Pd2(dba)3, tri-o-tolylphosphine, CuCl and excess of K 2CO3 in DMF followed by deprotection of the sulfonamide with 20% trifluoroaceticacid yielded 4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl) benzenesulfonamide or celecoxib (6) in 30% yield. However, under identical conditions, synthesis of [11C]celecoxib ([11C]6) was unsuccessful. Instead, trapping [11C]CH3I in an argon purged solution of catalytic amounts of Pd2(dba)3 and tri-o-tolylphosphine followed by the addition of the precursor 5 in DMF under argon and heating the mixture at 135°C for 4 min resulted in the incorporation of [11C]CH3 group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [ 11C]celecoxib in 40 min (EOB) and 8 ± 2% yield (EOB) along with a specific activity of 1080 ± 180 Ci/mmol (n = 6) (EOB). Copyright © 2005 John Wiley & Sons, Ltd.