An acyliminium ion approach towards the synthesis of β-substituted 3,4-dihydroisoquinolone propionates

Tetrahedron Letters

Volumn 38, Issue 33, 1997, Pages 5747-5750

  Fisher, Matthew J ^a   Gunn, Bruce P ^a   Um, Suzane ^a   Jakubowski, Joseph A ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ISOQUINOLINE DERIVATIVE; PROPIONIC ACID DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; METHODOLOGY; REACTION ANALYSIS;

EID: 0030845059     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01285-9     Document Type: Article

References (22)

1. For a recent review on IIb-IIIa antagonists see: a) Samanen, J. Ann. Rep. Med. Chem. 1996, 31, 91-100.
2. b) Ojima, I.; Chakravarty, S.; Dong, Q.; Biorg. & Med. Chem., 1995, 3, 337-360.
3. Fisher M. J.; Gunn B.P.; Harms, C.S.; Kline, A.D.; Mullaney, J.T.; Nunes, A.; Scarborough, R.M.; Arfstan, A.E.; Skelton, M.A.; Um. S.L.; Unerback, B.G.; Jakubowski, J.A. J. Med. Chem. In press.
4. This value represents the concentration required to reduce the binding of fibrinogen to purified human GP IIb-IIa by 50%. For details see reference 2.
5. An alternative approach for the construction β-amido esters would employ the Michael addition of amide anions to acrylates. Interesting protocol for this type of transformation has been recently disclosed. Ahn, K.H.; Lee, S.J. Tetrahedron Lett. 1994, 35, 1875-1878.
6. For a review of acyliminium ion chemistry see: Speckamp, N.W.; Hiemstra, H. Comprehensive Organic Synthesis; Trost, B.M.; Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 2, pp. 1049-1082.
7. a) Speckamp, W.N.; Hiemstra, H. Tetrahedron 1985, 41, 4367-4416.
8. b) Speckamp, W.N. Recl. Trav. Chem. Prog. Pays-Bas 1981, 100, 345.
9. c) Zaugg, H.E. Synthesis 1984, 85, 181.
10. For exocyclic reduction efforts see: Moeller, K.D.; Hanau, C.; Tetrahedron Lett. 1992, 33, 6041-6044.
11. For endocyclic reduction efforts see: a) Langlois, N.; Favre, F.; Rojas, A. Tetrahedron Lett. 1993, 34, 4635-4638.
12. b) Fisher, M.J.; Overman, L.E., J. Org. Chem. 1990, 55, 1447-1459.
13. For leading references see: a) Shono, T.; Matsumura, Y.; Uchida, K.; Kobayashi, H.; J. Org. Chem. 1985, 50, 3243-3245.
14. b) Mori, M.; Uozumi, Y.; Kimura, M.; Ban, Y.; Tetrahedron, 1986, 42, 3793-3806.
15. c) Reisch, J.; Bathe, A.; Rosenthal, B.H.N.; Salehiartimani, R.A. J. Heterocyclic Chem. 1987, 24, 869-872.
16. Iminium salts have been prepared by the reaction of an α-chloro ether with an amine. See: Jahn, U.; Schroth W. Tetrahedron Lett. 1993, 34, 5863-5866.
17. All new compounds provided satisfactory spectroscopic and analytical data.
18. 6 benzyloxy group.
19. All reported yields are unoptimized.
20. 4) and concentrated. Chromatography on silica gel, eluting with hexanes/EtOAc, provided intermediates 10 in good yield.
21. 4) and concentrated. Chromatography on silica gel, eluting with hexanes/EtOAc, provided phenyl substituted intermediates 10 in good yield.
22. 4) and concentrated. The crude product was purified on silica gel eluting with hexanes/EtOAc which provided the desired products in moderate to good yield.