Rhodium‐mediated [¹¹C]carbonylation: a library of N‐phenyl‐N′‐{4‐(4‐quinolyloxy)‐phenyl}‐[¹¹C]‐urea derivatives as potential PET angiogenic probes

Abstract

aÃAs part of our ongoing investigation into the imaging of angiogenic processes, a small library of eight vascular endothelial growth factor receptor-2 (VEGFR-2)/platelet-derived growth factor receptor b dual inhibitors based on the N-phenyl-N 0 -4-(4-quinolyloxy)-phenyl-urea was labelled with 11 C (b 1 , t 1/2 = 20.4 min) in the urea carbonyl position via rhodium-mediated carbonylative cross-coupling of an aryl azide and different anilines. The decay-corrected radiochemical yields of the isolated products were in the range of 38-81% calculated from 11 C]-urea (2.1 GBq) was isolated after total reaction time of 45 min with a specific activity of 9274 GBq mmol À1 .

Transition metal mediated synthesis using [11C]CO at low pressure – a simplified method for 11C‐carbonylation

“…The radiochemical yield was not significantly affected when the reaction volume was reduced to 250 μL while keeping the same reagent concentration (32%, n = 1). The high conversion of [ 11 C]CO was in line with what generally has been reported for Rh(I) mediated 11 C‐carbonylations conducted with the high pressure method . The [ 11 C]CO conversion still remained high (90%, n = 1) when the reaction temperature was lowered to 100°C, but the product selectivity dropped significantly (7%, n = 1), possibly because of the reduced reactivity of the deactivated 3,4‐dichloroaniline at lower temperature and consequently more remaining rhodium‐[ 11 C]carbonyl species at the end of reaction.…”

“…Ureas labelled in the carbonyl position can be efficiently synthesised by 11 C‐carbonylation of organoazides to form isocyanate intermediates, as proposed by Doi et al ., which subsequently reacts with amines . The key advantage of using [ 11 C]CO over amination of [ 11 C]phosgene is that unsymmetrical [ 11 C]ureas can be readily obtained.…”

11CO bonds made easily for positron emission tomography radiopharmaceuticals

“…154 Rh(I) catalysts, for example, have been deployed to produce small collections of 11 C-ureas by aminocarbonylation in the presence of aryl or sulfonyl azides, including VEGFR-2 ligands. 155,156 …”

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…[58] This method was applied in the preparation of aw ide range of 11 C-labeled compounds,i ncluding 11 C-labeled VEGFR-2/ PDGFR-b dual inhibitors, [59] [ 11 C]phenytoin, [60] 11 C-labeled sulfonyl ureas and carbamates, [61,62] and 11 C-labeled hydroxyurea derivatives. [58] This method was applied in the preparation of aw ide range of 11 C-labeled compounds,i ncluding 11 C-labeled VEGFR-2/ PDGFR-b dual inhibitors, [59] [ 11 C]phenytoin, [60] 11 C-labeled sulfonyl ureas and carbamates, [61,62] and 11 C-labeled hydroxyurea derivatives.…”