Combinatorial synthesis of indolizines on solid support

Tetrahedron Letters

Volumn 40, Issue 50, 1999, Pages 8741-8745

  Goff, Dane A ^a,b  

^a NOVARTIS PHARMA AG   (Switzerland)

^b RIGEL PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHALCONE; INDOLIZINE DERIVATIVE; PHENAZOPYRIDINE;

ARTICLE; CHEMICAL STRUCTURE; CYCLIZATION; MOLECULAR MODEL; OXIDATION; REACTION ANALYSIS; SYNTHESIS;

EID: 0033544818     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01879-1     Document Type: Article

References (18)

1. For a review of pyridinium ylide chemistry, see: Sliwa, W. Heterocycles 1986, 24, 181-219. For alternative preparations of indolizines, see: Uchida, T.; Matsumoto, K. Synthesis 1976, 209-236; Molina, P.; Fresneda, P. M.; Lajara, M. C. J. Heterocyclic Chem. 1985, 22, 113-119.
2. For a review of pyridinium ylide chemistry, see: Sliwa, W. Heterocycles 1986, 24, 181-219. For alternative preparations of indolizines, see: Uchida, T.; Matsumoto, K. Synthesis 1976, 209-236; Molina, P.; Fresneda, P. M.; Lajara, M. C. J. Heterocyclic Chem. 1985, 22, 113-119.
3. For a review of pyridinium ylide chemistry, see: Sliwa, W. Heterocycles 1986, 24, 181-219. For alternative preparations of indolizines, see: Uchida, T.; Matsumoto, K. Synthesis 1976, 209-236; Molina, P.; Fresneda, P. M.; Lajara, M. C. J. Heterocyclic Chem. 1985, 22, 113-119.
4. (a) Tsuge, O.; Kanemasa, S.; Takenaka, S. Heterocycles 1983, 20, 1907-1912.
5. (b) Tsuge, O.; Kanemasa, S.; Takenaka, S. J. Org. Chem. 1986, 51, 1853-1855.
6. (c) Tsuge, O.; Kanemasa, S.; Takenaka, S.; Kuraoka, S. Chemistry Lett. 1984, 465-468.
7. (a) Katritzky, A. R.; Grzeskowiak, N. E.; Alvarez-Builla, J. J. Chem. Soc., Perkin Trans. 1 1981, 1180-1185.
8. (b) Katritzky, A. R.; Grzeskowiak, N. E.; Alvarez-Builla, J.; Tarraga-Tomas, A. J. Praktische Chem. 1983, 177-187.
9. Gubin, J.; Lucchetti, J.; Mahaux, J.; Nisato, D.; Rosseels, G.; Clinet, M.; Polster, P.; Chatelain, P. J. Med. Chem. 1992, 35, 981-988.
10. (a) Nugent, R. A.; Murphy, M. J. Org. Chem. 1987, 52, 2206-2208.
11. (b) Rosseels, G.; Inion, H.; Matteazzi, J. R.; Peiren, M.; Prost, M.; Deschamps, M.; Tornay, C.; Colot, M.; Charlier, R. Eur. J. Med. Chem. Chim. Ther. 1975, 10, 579-584.
12. HPLC utilized a Vydac analytical C-18 RP column with a gradient of 0-80% acetonitrile with water containing 0.1% trifluoroacetic acid over 40 min. Detection was at 214 nm, flow rate=1.0 mL/min.
13. 1H NMR of several of the crude mixtures gave the following ratio of diastereomers: 3a (20:1), 3e (4:1), 3f (5:1) and 3g (1:1).
14. (a) Wei, X.; Hu, Y.; Li, T.; Hu, H. J. Chem. Soc., Perkin Trans. 1 1993, 2487-2489.
15. (b) Hu, Y.; Hu, H. Synth. Comm. 1992, 22, 1491-1496.
16. (c) Wei, X.; Hu, Y.; Li, T.; Hu, H. Synth. Comm. 1992, 22, 2103-2109.
17. After this work had been completed, Wei and co-workers reported the first direct synthesis of -acylindolizines using α,β-unsaturated ketones. See: Zhang, X.; Cao, W.; Wei, X.; Hu, H. Synth. Comm. 1997, 27, 1395-1403.
18. 2O to give 3d as a solid (15.1 mg). HPLC (gradient 0-80% acetonitrile in water with 0.1% TFA over 40 min) rt=26.4 min. The remainder of the resin was treated as above except that 50 mg of TPCD was included and the reaction was run for 2 h at 80°C. After the initial lyophilization the crude product was dissolved in acetonitrile and passed down a short column of Grade V neutral alumina. After concentration in vacuo, the material was lyophilized to give a light green solid 4d (8.8 mg). HPLC rt=33.0 min.