A novel and regioselective pyridine-ring formation by Lewis acid-induced cyclisation of 2-(N-allylbenzylamino)-3-[2,2-bis(ethoxycarbonyl)vinyl]pyrido[1,2-a]pyrimidin-4(4H)-one

Abstract

The Lewis acid-induced cyclisation of 2-(N++ -allylbenzylamino)-3-[2,2-bis(ethoxycarbonyl)vinyl]pyrido[1,2-++ a]pyrimidin-4(4H)-one 1a, which provides a novel and regioselective synthetic approach to the fused pyridine-ring, is described for the first time.

References

1. M. Noguchi, T. Sunagawa, R. Akao, A. Kakehi and H. Yamamoto, unpublished work.
2. In order to prepare selectively the vinyl substrates, modified Knoevenagel reaction conditions [CH₂(CO₂Et)₂(1.1 equiv.), benzene, piperidine (2.0 equiv.), AcOH (2.0 equiv.), reflux, 7–18 h] were employed to afford the desired substrates in 38–72% yields. A. C. Cope, C. M. Hofmann, C. Wyckoff and E. Hardenbergh, J. Am. Chem. Soc., 1941, 63, 3452.
3. All new products in this study were fully characterised by spectroscopic and microanalytical data.
4. The “tert-amino effect” refers inherently to a cyclisation process thermally induced. For recent reviews see: W. Verboom and D. N. Reinhoudt, Recl. Trav. Chim. Pays-Bas, 1990, 109, 311; O. Meth-Cohn, “Advances in Heterocyclic Chemistry”, ed. A. R. Katritzky, Academic Press, vol. 65, 1996, pp. 1–37.
5. In some of the cases extensively investigated by Reinhoudt and co-workers, the use of a Lewis acid (ZnCl₂) accelerated the reaction rate and/or affected the diastereoselectivity of the cyclisation products;; D. N. Reinhoudt, G. W. Visser, W. Verboom, P. H. Benders and M. L. M. Pennings, J. Am. Chem Soc., 1983, 105, 4775; W. Verboom, D. N. Reinhoudt, R. Visser and S. Harkema, J. Org. Chem., 1984, 49, 269.
6. W. Verboom, B. H. M. Lammerink, R. J. M. Egberink, D. N. Reinhoudt and S. Harkema, ibid., 1985, 50, 3797.