Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-21
2003-02-04
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S189000, C514S314000, C514S316000
Reexamination Certificate
active
06515130
ABSTRACT:
BACKGROUND OF THE INVENTION
Field of the Invention
The invention relates to a process of preparing [S-(R*,S*)]-&bgr;-[[[1-[1-oxo-3-(4-piperidinyl)propyl]-3-piperidinyl]carbonyl]amino]-3-pyridinepropanoic acid derivatives represented by the formula
wherein R
1
and R
2
are independently selected from hydrogen, lower alkyl and halogen.
The compounds of formula I and method of making and using the compounds of formula I are described in WO 97/41102, Nov. 6, 1997.
Compounds of formula I are antagonists of the platelet fibrinogen receptor (GP 11b/111a antagonist). Thus, the compounds of formula I are useful for the treatment of thrombotic disorders such as restenosis post-angioplasty, unstable/stable angina and myocardial infarction.
A known method of the preparation of a compound of formula I is disclosed in WO 97/41102 involving coupling of enantiomerically enriched methyl (S)-3-amino-3-pyridylpropanoate with N-(t-butoxycarbonyl)-(R)-nipecotic acid followed by removal of the N-t-butoxycarbonyl protecting group under acidic conditions and coupling with 3-(N-t-butoxycarbonyl-4-piperidyl)propionic acid. The crude ester product is then hydrolyzed using aqueous LiOH and the N-t-butoxycarbonyl amino protecting group is removed under acidic conditions with trifluoroacetic acid (“TFA”). The bis-TFA salt is isolated as a white amorphous solid.
A process for preparing N-(3-piperidinyl carbonyl)-&bgr;-alanine derivatives is disclosed in WO 95/08536.
The current invention relates to a more efficient process of preparing compounds of formula I.
REFERENCES:
patent: 4585887 (1986-04-01), Jolidon et al.
patent: 5254573 (1993-10-01), Bovy et al.
patent: 5840961 (1998-11-01), Behling et al.
patent: WO 95/08536 (1995-03-01), None
patent: WO 97/41102 (1997-11-01), None
patent: WO98/02410 (1998-01-01), None
Hoekstra et al. “Solid phase parallel synthesis applied to . . . ” Bioorg. Med. Chem. Let. v.6, 2371-2376 (1996).*
J.G. Rico, R.J. Lindmark, T.E. Rogers, & P.R. Bovy, A Highly Stereoselective Michael Addition to an a,&bgr;-Unsaturated Ester as the Crucial Step in the Synthesis of a Novel &bgr;-Amino Acid-Containing Fibrinogen Receptor Antagonist, J. Org. Chem. 1993, 58,7948-7951.
F.A. Davis, J.M. Szewczyk & R.E. Reddy, An Efficient Synthesis of (S)—(+) -Ethyl &bgr;-Amino-3-pyridinepropanoate Using Enantiopure Sulfinimines, J. Org. Chem. 1996, 61, 2222-2225.
T.P. Tang & J.A. Ellman, The tert-Butanesulfinyl Group: An Ideal Chiral Directing Group and Boc-Surrogate for the Asymmetric Synthesis and Applications of &bgr;-Amino Acids, J. Org. Chem. 1999, 64, 12-13.
M.A. Croucher, B.S. Meldrum, & P. Krogsgaard-Larsen, Anticonvulsant Activity of GABA Uptake Inhibitors and Their Prodrugs Following Central or Systemic Administration, European Journal of Pharmacology, 89 (1983) 217-228.
D.L. Lee, C.J. Morrow, & H. Rapport, &agr;-Methylenelactam Rearrangement, J. Org. Chem., vol. 39, No. 7, 1974, 893-902.
N.J. Leonard & D. Choudhur, &ggr;-Pyrones by Isomerization. Substituted 3,5-Dibenzyl-4H-pyran-4-ones, Noyes Chemical Laboratory, University of Illinois, vol. 79, (1957) 156-160.
Akkerman, A.M., De Jong, D.K. and Vaeldstra, H., Synthetic Oxytocics. 1. 3-(Piperidyl-(N)-Methyl)-Indoles and Related Compounds,Rec. Trav. Chim Pays-Bas, 1951, 70 p. 8899-916.
William J. Hoekstra et al., Solid-Phase Parallel Synthesis Applied to Lead Optimization: Discovery of Potent Analogues of the GPIIb/IIIa Antagonist RWJ-50042, Bioorganic Medical Chemistry Letters, vol. 6, no. 20, 1996, pp. 2371-2376.
William J. Hoekstra et al., Solid Phase Synthesis Via N-Terminal Attachment to the 2-Chlorotrityl Resin, Tetrahedron Letters, vol. 38, no. 15, 1997, pp. 2629-2632.
Cohen Judith H.
Justus Michael
Maryanoff Cynthia A.
Rössler Armin
Schröder Fridtjof
LandOfFree
Process for preparing... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3180732