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Synthesis of [ 11 C]celecoxib: a potential PET probe for imaging COX‐2 expression
Author(s) -
Prabhakaran Jaya,
Majo Vattoly J.,
Simpson Norman R.,
Van Heertum Ronald L.,
Mann J. John,
Kumar J. S. Dileep
Publication year - 2005
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1002
Subject(s) - celecoxib , chemistry , yield (engineering) , iodide , sulfonamide , trifluoroacetic acid , catalysis , medicinal chemistry , methyl iodide , chemical synthesis , ibuprofen , stereochemistry , nuclear chemistry , organic chemistry , in vitro , pharmacology , biochemistry , medicine , materials science , metallurgy
[ 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.