An asymmetric synthesis of (R)-5-(methylamino)-5,6-dihydro-4H-imidazo-[4,5,1-ij]quinolin-2(1H)-one (1) and its [2-14C]- and [6,7-3H2]-labeled forms

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 38; no. 12; pp. 1087 - 1098
• Main Authors: Heier, Richard F., Moon, Malcolm W., Stolle, Wayne T., Easter, John A., Hsi, Richard S. P.
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Ltd 01.12.1996; Wiley
• Subjects: asymmetric synthesis; Biochemical Research Methods; Biochemistry & Molecular Biology; carbon-14; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; D2 dopamine agonist; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; imidazoquinolinone; Life Sciences & Biomedicine; Organic chemistry; Pharmacology & Pharmacy; Physical Sciences; Preparations and properties; radioligand; Science & Technology; tritium; imidazoquinolinone; tritium; radioligand; carbon-14; asymmetric synthesis; D2 dopamine agonist; Agonist; Radiolabelling; Angular nitrogen heterocycle; Carbon Isotopes; Tritium; Hydrogen Isotopes; Tricyclic compound; Carbonyl Chlorides; D2 Dopamine receptor; Asymmetric synthesis; Bicyclic compound; Ureas; Chemical synthesis; Carbon 14
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/(SICI)1099-1344(199612)38:12<1087::AID-JLCR933>3.0.CO;2-O

(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 [14C]phosgene to provide a two‐step synthesis of 1 labeled with carbon‐14 at the C‐2 position (236 μCi/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.