J. Kumar, V. J. Majo, J. Prabhakaran
Oct 15, 2003
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Influential Citations
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Journal
Journal of Labelled Compounds and Radiopharmaceuticals
Abstract
A convenient synthesis of [N-methyl-11C]-3-[(6-dimethylamino)pyridin-3-yl]-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidine-7-amine (R121920), a highly selective CRF1 antagonist has been developed as a potential PET ligand. 3 - [(6 - methylamino)pyridin - 3 - yl]-2,5-dimethyl-N,N-dipropylpyrazolo [1,5-a]pyrimidine-7-amine (7), the precursor for radiolabelling was synthesized through a novel palladium catalyzed Suzuki coupling of aryl bromide 5 with heteroaryl boronate ester 4. The requisite boronate ester 4 was synthesized in four steps from 2-amino-4-bromopyridine in 50% overall yield. Although the synthesis of cold R121920 proceeded in 93% yield by sodium hexamethyl-disilazide (NaHMDS) mediated N-methylation of the desmethylamine 7 at −78°C, the attempted radiosynthesis under various conditions using conventional bases were not successful. However, the radiolabeling of [11C]R121920 was successfully carried out with [11C]MeOTf in acetone at −20°C in the absence of added basic reagents. The radiotracer was purified by RP-HPLC followed by RP-solid phase extraction. The yield of the reaction was 5% (at EOB) and the specific activity was >1000 Ci/mmol (at EOB) with a radiochemical purity >99%. Copyright © 2003 John Wiley & Sons, Ltd.