Synthesis of 11C-labelled amides by palladium-mediated carboxamination using [11C]Carbon monoxide, in situ activated amines and 1,2,2,6,6-pentamethylpiperidine

Twenty-seven C-11-labelled amides were synthesised using [C-11]carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro-autoclave (200 muL). The focus of the study was to improve the radiochemical yields in this palladium-mediated amide synthesis when employing less-reactive amines, such as methylamine, [(2R)-1-ethylpyrrohdin-2-yl]methylamine (40) and 2-(pyridin-2-yl)ethanamine (41). The radiochemical yields were improved when utilizing 1,2,2,6,6-pentamethylpiperidine (pempidine) in combination with the amine substrates. The C-11-labelled amides were obtained mostly in high radiochemical yields (in the range 16-94%) and the specific radioactivity varied between 650 and 1250 GBq/mumol. 1-(1,3-Benzodioxol-5-yl[C-13]carbonyl)piperidine (6a) was synthesised to verify the labelling position (delta = 169.8 ppm) using C-13 NMR spectroscopy. The radiochemical purity of the target compounds was determined by analytical HPLC and exceeded 95%. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).