Optimisation, scope and limitations of the synthesis of 5-aminoindolizines from oxazolo[3,2-a]pyridinium salts

Tetrahedron Letters

Volumn 47, Issue 3, 2006, Pages 261-265

  Tielmann, P ^a   Hoenke, C ^a  

^a Boehringer Ingelheim GmbH and Co KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACETONITRILE; INDOLIZINE DERIVATIVE; PYRIDINIUM DERIVATIVE; SOLVENT;

ARTICLE; CHEMICAL REACTION KINETICS; DRUG STABILITY; DRUG SYNTHESIS; HEATING; MICROWAVE RADIATION; STEREOSPECIFICITY;

EID: 28844435263     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2005.11.033     Document Type: Article

References (36)

1. Two alkaloids containing an indolizine nucleus within a fused ring system have been reported: W. Flitsch A.R. Katritzky C.W. Ress Comprehensive Heterocyclic Chemistry Vol. 4 1984 Pergamon Oxford 476
2. W. Chai, J.G. Breitenbucher, A. Kwok, X. Li, V. Wong, N.I. Carruthers, T.W. Lovenberg, C. Mazur, S.J. Wilson, F.U. Axe, and T.K. Jones Bioorg. Med. Chem. Lett. 13 2003 1767
3. L.-L. Gundersen, A.H. Negussie, and O.B. Østby Arch. Pharm. Pharm. Med. Chem. 336 2003 191
4. S.P. Gupta, A.N. Mathur, A.N. Nagappa, D. Kumar, and S. Kumaran Eur. J. Med. Chem. 38 2003 867
5. L.-L. Gundersen, K.E. Malterud, A.H. Negussie, F.R. Rise, S. Teklu, and O.B. Østby Bioorg. Med. Chem. 11 2003 5409
6. S. Teklu, L.-L. Gundersen, T. Larsen, K.E. Malterud, and F. Rise Bioorg. Med. Chem. 13 2005 3127
7. O.B. Østby, B. Dalhus, L.-L. Gundersen, F. Rise, A. Bast, and G.R.M.M. Haenen Eur. J. Org. Chem. 2000 3763
8. P. Wang, Z. Zhang, X. Ma, Y. Huang, X. Liu, P. Tu, and T. Tong Mech. Ageing Dev. 124 2003 1025
9. S. Medda, P. Jaisankar, R.K. Manna, B. Pal, V.S. Giri, and M.K. Basu J. Drug Target 11 2003 123
10. L.D. Bolle, G. Andrei, R. Snoeck, Y. Zhang, A.V. Lommel, M. Otto, A. Bousseau, C. Roy, E.D. Clercq, and L. Naesens Biochem. Pharmacol. 67 2004 325
11. M. Scholtz Ber. Dtsch. Chem. Ges. 45 1912 734
12. V. Boekelheide, and R.J. Windgassen Jr. J. Am. Chem. Soc. 81 1959 1456
13. A.E. Tschitschibabin Ber. Dtsch. Chem. Ges. 60 1927 1606
14. J. Hurst, T. Melton, and D.G. Wibberley J. Chem. Soc. 1965 2948
15. G. Jones, and J. Stanyer J. Chem. Soc. C 1969 901
16. Y. Miki, H. Hachiken, and S. Takemura Heterocycles 22 1984 701
17. A. Padwa, D.J. Austin, L. Precedo, and L. Zhi J. Org. Chem. 58 1993 1144
18. G. De Bue, and J. Nasielski Bull. Soc. Chim. Belg. 106 1997 97
19. A.R. Katritzky, G. Qiu, B. Yang, and H.-Y. Ye J. Org. Chem. 64 1999 7618
20. K. Sarkunam, and M. Nallu J. Heterocycl. Chem. 42 2005 5
21. X. Wei, Y. Hu, T. Li, and H. Hu J. Chem. Soc., Perkin Trans. 1 1993 2487
22. X. Fang, Y.-M. Wu, J. Deng, and S.W. Wang Tetrahedron 60 2004 5487
23. A.V. Kel'in, A.W. Sromek, and V. Gevorgyan J. Am. Chem. Soc. 123 2001 2074
24. J.T. Kim, and V. Gevorgyan Org. Lett. 4 2002 4697
25. C.-H. Park, V. Ryabova, I.V. Seregin, A.W. Sromek, and V. Gevorgyan Org. Lett. 6 2004 1159
26. E.V. Babaev, and A.V. Efimov Chem. Heterocycl. Compd. 33 1997 875
27. E.V. Babaev, A.V. Efimov, D.A. Maiboroda, and K. Jug Eur. J. Org. Chem. 1998 193
28. E.V. Babaev, A.V. Efimov, S.G. Zhukov, and V. Rybakov Chem. Heterocycl. Compd. 34 1998 852
29. The construction of indolizine libraries has recently been reported: Z. Chen, G. Yue, C. Lu, and G. Yang Synlett 2004 1231
30. G. Yue, Y. Wan, S. Song, G. Yang, and Z. Chen Bioorg. Med. Chem. Lett. 15 2005 453
31. The reaction mixture was poured onto ice and not diluted with water and the product was precipitated at room temperature.
32. This type of reactivity has already been observed: C.K. Bradsher, and M.F. Zinn J. Heterocycl. Chem. 4 1967 66
33. V.I. Terenin, E. Kabanova, E. Feoktistova, and Y.G. Bundel' Chem. Heterocycl. Compd. 28 1992 766
34. Since the effect of applying higher temperature and longer reaction times on the yield was marginal, we decided to choose the milder and faster conditions as 'best' result.
35. Typical procedure: 100 mg (291 μmol) of 3b were dissolved in 2 ml acetonitrile, whereafter 71 mg (581 μmol) DMAP and 31.6 μl (320 μmol) of piperidine were added. The reaction mixture was heated for 1 h to 100°C in a microwave oven (CEM Discover™, max 300 W, for details see Supplementary material) and poured into 10 ml of water. Most of the yellow product precipitated after standing at rt overnight so that the supernatant could be decanted. The residue was carefully washed with water and dissolved in ethyl acetate. The supernatant was centrifuged for 1 h at 3000 rpm, whereafter some more product could be obtained after decantation and washing with water. This second crop was also dissolved in ethyl acetate and the combined organic layer was dried with sodium sulfate. After removal of the solvent the product was isolated in approx. 95% purity. Yield: 58 mg (61%).
36. For analytical data of all isolated 5-aminoindolizines see Supplementary material.