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

Journal of Labelled Compounds and Radiopharmaceuticals

Volumn 38, Issue 12, 1996, Pages 1087-1098

  Heier, Richard F ^a   Moon, Malcolm W ^a   Stolle, Wayne T ^a   Easter, John A ^a   Hsi, Richard S P ^a  

^a PFIZER INC   (United States)

Author keywords

Asymmetric synthesis; Carbon 14; D2 dopamine agonist; Imidazoquinolinone; Radioligand; Tritium

Indexed keywords

AMINES; CARBON; NEUROPHYSIOLOGY; SYNTHESIS (CHEMICAL);

ASYMMETRIC EPOXIDATION; ASYMMETRIC SYNTHESIS; CARBON 14; D2 DOPAMINE AGONIST; DOPAMINE; IMIDAZOQUINOLINONE; NITROQUINOLINES; PARKINSON'S DISEASE; POTENTIAL DRUG; RADIOLIGANDS;

TRITIUM;

CARBON 14; DOPAMINE RECEPTOR STIMULATING AGENT; TRITIUM;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ISOTOPE LABELING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RADIOCHROMATOGRAPHY; REACTION ANALYSIS;

TRITIUM;

EID: 0029804905     PISSN: 03624803     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-1344(199612)38:12<1087::AID-JLCR933>3.0.CO;2-O     Document Type: Article

References (13)

1. Moon, M. W.; Morris, J. K.; Heier, R. F.; Hsi, R. S. P.; Manis, M. O.; Royer, M. E.; Walters, R. R.; Lawson, C. F.; Smith, M. W.; Lahti, R. A.; Piercey, M. F.; Sethy, V. H. Drug Design and Discovery, 1992. 9, 313-322.
2. Moon M. W.; Hsi, R. S. P. Journal of Labelled Compounds and Radiopharmaceuticals, 1992, 31, 933-943.
3. Heier, R. F.; Dolak, L. A.; Duncan, J, N.; Hyslop, D.K.; Lipton, M. J.; Martin, I. J.; Mauragis, M. A.; Piercey, M. F.; Smith, M. W.; Nichols, N. F.; Schreur, P. J. K. D.; Moon, M. W. J. Med. Chem., submitted
4. Rao, K. V.; Jackman, D. J. Het. Chem., 1970, 10, 213-215.
5. Jacobsen, E. N. In Catalytic Asymmetric Synthesis; Ojima. I, Ed.; VCH Publishers, Inc., New York, NY (1993). pp 159-202.
6. 7 has a higher melting point (153-156 °C) than the enantiomer. Crystallization of the chiral epoxide (96% ee) did not improve its optical purity.
7. Payne, G. B.; Deming, P. H.; Williams, P. H. J. Org. Chem., 1961, 26, 659-663.
8. The enantiomeric series of compounds has also been prepared by the same procedure from 3 by using (R,R)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane- diaminomanganese(III) chloride as the catalyst; chiral HPLC retention times of the various intermediates are presented in the experimental section.
9. Byproducts in the synthesis arise by intramolecular rearrangement of the propionyl group to the 3-hydroxy position [(3R-trans)-1,2,3,4-tetrahydro-N-methyl 8-nitro-3-(propionyloxy)-4-quinolinamine, 8%) and to the 4-methylamine position [(3R-trans)-1,2,3,4-tetrahydro-4-propionylamino-8-nitro-3-quinolinol, 3%); a small amount of the hydroysis product 6 is also formed in this reaction. Intramolecular rearrangement to the 4-position is also encountered in the base-induced hydrolysis of 5 (see experimental section).
10. Pfister, J. R. Synthesis, 1984, 969.
11. Treatment of 7 in aqueous THF with 1.5 eq of perchloric acid immediately opened the aziridine ring giving a 1:2 mixture of amino alcohols [(3S-cis)- and (3R-trans)-1,2,3,4-tetrahydro-3-methylamino-8-nitro-4-quinolinol).
12. Supplied by Amersham Corporation, Arlington Heights, IL (Lot No. CFQ 8282)
13. Reduction was carried out at the National Tritium Labeling Facility (NTLF), Lawrence Berkeley Laboratory, University of California, Berkeley, CA.