An asymmetric synthesis of (R)-5-(methylamino)-5,6-dihydro-4H-imidazo-[4,5,1-ij] quinolin-2(1H)-one (1) and its [2-C-14]- and [6,7-H-3(2)]-labeled forms.

(R)-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 Parkinson's disease. An asymmetric epoxidation approach has been used to prepare 1 in eleven steps (15% overall yield) from 8-nitroquinoline. An advanced intermediate in this synthesis, tert-butyl (R)-methyl(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 are useful in drug disposition and receptor binding studies, this approach also provides a convenient synthesis for the unlabeled form of drug.