AN ASYMMETRIC-SYNTHESIS OF -5-(METHYLAMINO)-5,6-DIHYDRO-4H-IMIDAZO-[4,5,1-IJ] QUINOLIN-2(1H)-ONE(1) AND ITS [2-C-14]-LABELED AND [6,7-H-3(2)]-LABELED FORMS

)-5-(Methylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij] quinolin-2(1H)-one (1) is a dopamine agonist which shows selectivity for the D2 receptor subtype, and is of interest as a potential drug for the treatment of P arkinson's disease. An asymmetric epoxidation approach has been used t o prepare 1 in eleven steps (15% overall yield) from 8-nitroquinoline. An advanced intermediate in this synthesis, tert-butyl (8-amino-1,2,3 ,4-tetrahydro-3-quinolinyl)carbamate (10), has been reacted with [C-14 ]phosgene to provide a two-step synthesis of 1 labeled with carbon-14 at the C-2 position (236 mu Ci/mg). Bromination of 1 gave the dibromo analogue 12b which was reduced in the presence of tritium gas to give 1 labeled with tritium at the C-6 and C-7 positions (28.5 Ci/mmol). In addition to providing syntheses for labeled forms of the drug which a re useful in drug disposition and receptor binding studies, this appro ach also provides a convenient synthesis for the unlabeled form of dru g.