Abstract
The novel CCK‐A agonist, (S)‐3‐(3‐{1‐[(isopropylphenylcarbamoyl)methyl]‐2,4‐dioxo‐5‐phenyl‐2,3,4,5‐tetrahydro‐1H‐benzo[b][1,4]diazepin‐3‐yl}ureido)benzoic acid, GI181771 ((S)‐1) has been isotopically labelled with carbon‐11 at its urea site using [^11^C]phosgene in a one‐pot two‐step process, via the intermediate preparation of an [^11^C]isocyanate derivative. Optimized conditions for the preparation of (S)‐[^11^C]‐1 were the following: (1) Trapping of [^11^C]phosgene (radiosynthesized from cyclotron‐produced [^11^C]methane via [^11^C]carbon tetrachloride using minor modifications of published processes) at room temperature for 1–2 min in 300 µl of acetonitrile containing 0.6 µmol of the appropriate (structurally complex) chiral‐amine giving the corresponding [^11^C]isocyanate followed by (2) addition of an excess of 3‐aminobenzoic acid (40 µmol in 100 µl of THF) as the second amine giving the desired urea derivative (S)‐[^11^C]‐1 and (3) high‐performance liquid chromatography (HPLC) purification on a semi‐preparative Waters Symmetry® C18. Starting from a typical 1.2 Ci (44.4 GBq) batch of [^11^C]methane, 25–35 mCi (0.92–1.29 GBq, 6.8–9.6% decay‐corrected yield based on starting [^11^C] methane, n = 5) of (S)‐[^11^C]‐1 could be obtained within 35 min of radiosynthesis (HPLC purification and formulation as an i.v. injectable solution using a home‐made Sep‐pak®Plus C18 device included) with specific radioactivities ranging from 500 to 1500 mCi/µmol (18.5–55.5 GBq/µmol). The radiotracer preparation was a clear and colourless solution and its pH was between 5 and 7. As demonstrated by HPLC analysis, the radiolabelled product was found to be >99% chemically and radiochemically pure and the preparation was shown to be free of non‐radioactive precursors (starting amines) and radiochemically stable for at least 60 min. Finally, enantiomeric purity was found to be >99% according to chiral HPLC, demonstrating the absence of racemization during the process. Copyright © 2005 John Wiley & Sons, Ltd.