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

[ 11 C]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)phenylmethyl]‐4‐[5‐(4‐tributylstannylphenyl)‐3‐trifluoromethylpyrazol‐1‐yl]benzenesulfonamide ( 5 ) with methyl iodide in presence of catalytic amounts of Pd 2 (dba) 3 , tri‐ o ‐tolylphosphine, CuCl and excess of K 2 CO 3 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 [ 11 C]celecoxib ([ 11 C] 6 ) was unsuccessful. Instead, trapping [ 11 C]CH 3 I in an argon purged solution of catalytic amounts of Pd 2 (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 [ 11 C]CH 3 group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [ 11 C]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.