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An asymmetric synthesis of ( R )‐5‐(methylamino)‐5,6‐dihydro‐4 H ‐imidazo‐[4,5,1‐ ij ]quinolin‐2(1 H )‐one (1) and its [2‐ 14 C]‐ and [6,7‐ 3 H 2 ]‐labeled forms
Author(s) -
Heier Richard F.,
Moon Malcolm W.,
Stolle Wayne T.,
Easter John A.,
Hsi Richard S. P.
Publication year - 1996
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199612)38:12<1087::aid-jlcr933>3.0.co;2-o
Subject(s) - chemistry , stereochemistry , medicinal chemistry , bicyclic molecule
( R )‐5‐(Methylamino)‐5,6‐dihydro‐4 H ‐imidazo[4,5,1‐ ij ]quinolin‐2(1 H )‐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 [ 14 C]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.