Abstract :
A straightforward approach to novel 2-dialkylamino-4H-pyrido[1,2-a][1,3,5]triazin-4-ones synthesis is presented. The construction of these compounds was achieved by one-pot synthesis involving condensation of 2-aminopyridine or 2-aminopicolines with ethoxycarbonylisothiocianate, followed by amination of the thioureas, and finally thermal ring closure of resulting guanidines. This allowed access to the unreported title heterocycles. We described an efficient, facile, one-pot synthesis of a novel 2-dialkylamino-4H-pyrido[1,2-a][1,3,5]triazin-4-ones in order to obtain a library of pyridotriazines which will be used as building blocks in medicinal chemistry.
Keywords :
Heterocycles, Infrared and Masse Spectroscopy, NMR spectroscopy, pyridotriazines, Synthesis.References :
1. T. Tanaka, Y. Morishima, K. Watanabe, T. Shibutani, M. Yasuoka, and T. Shibano, “Combined effect of the 5-HT2 receptor antagonist DV-7028 and aspirin or heparin on coronary cyclic flow reductions in dogs,” Cardiovascular Research, vol. 27, pp. 1374-1379, 1993.
2. B. Zaleska, B. Trzewik, E. Stodolak, J. Grochowski, and P. Serda, “One-Pot Synthesis of 3, 4-Dihydro-2H-pyrido [1, 2-a][1, 3, 5] triazin-2-one Derivatives from N-(2′-Pyridinyl) benzoylacetamide and Nitrosobenzenes,” Synthesis, vol. 2004, pp. 2975-2979, 2004.
3. D. Pawlak, M. Adamkiewicz, J. Malyszko, A. Takada, M. Mysliwiec, and W. Buczko, “Vascular and cardiac effects of DV-7028, a selective, 5-HT2-receptor antagonist in rats,” Journal of Cardiovascular Pharmacology, vol. 32, pp. 266-273, 1998.
4. T. Shibano, T. Tanaka, Y. Morishima, M. Yasuoka, K. Watanabe, and F. Fujii, “Pharmacological profile of a new 5-hydroxytryptamine2 receptor antagonist, DV-7028,” Archives Internationales de Pharmacodynamie et de Therapie, vol. 319, pp. 114-128, 1992.
5. S. Sengupta, L. A. Sellers, H. B. Matheson, and T. P. D. Fan, “Thymidine phosphorylase induces angiogenesis in vivo and in vitro: an evaluation of possible mechanisms,” British Journal of Pharmacology, vol. 139, pp. 219-231, 2003.
6. A. Moghaddam and R. Bicknell, “Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity,” Biochemistry, vol. 31, pp. 12141-12146, 1992.
7. H. Oda, T. Hanami, T. Iwashita, M. Kojima, M. Itoh, and Y. Hayashizaki, “Synthesis of 5-acetyl-2-aminopyrrole C-deoxyribonucleoside,” Tetrahedron, vol. 63, pp. 12747-12753, 2007.
8. M. Jalilian and M. Zahedi-Tabrizi, “Spectra and structure of binary azeotropes V-acetone–cyclopentane,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 69, pp. 278-281, 2008.
9. M. Zupan, B. Stanovnik, and M. Tisler, “Heterocycles. XCVII. Pyridazines. LI. Synthetic approaches to pyridazino [2, 3-a]-1, 3, 5-triazines, a novel heterocyclic system,” The Journal of Organic Chemistry, vol. 37, pp. 2960-2963, 1972.
10. W. Zeghida, J. Debray, S. Chierici, P. Dumy, and M. Demeunynck, “Concise synthesis of 2-amino-4 (3 H)-quinazolinones from simple (hetero) aromatic amines,” The Journal of Organic Chemistry, vol. 73, pp. 2473-2475, 2008.
11. D. S. Dodd and Y. Zhao, “Solid-phase synthesis of N,N′-substituted acylguanidines,” Tetrahedron Letters, vol. 42, pp. 1259-1262, 2001.
12. N. Primas, H. El-Kashef, J.-C. Lancelot, A. Lesnard, R. H. Dodd, and S. Raulta, “Triazine-fused β-carbolines: a facile three-step, one-pot synthesis of novel 2-alkyl (aryl) amino and 2-dialkylamino-7H-[1,3,5] triazino [1’,2’:1,6] pyrido [3,4-b] indol-4-ones,” Arkivoc, vol. 11, pp. 163-176, 2010.
13. A. Caruso, J.-C. Lancelot, H. El-Kashef, M. S. Sinicropi, R. Legay, A. Lesnard, et al., “A rapid and versatile synthesis of novel pyrimido [5, 4-b] carbazoles,” Tetrahedron, vol. 65, pp. 10400-10405, 2009.
14. M. Kopp, J. C. Lancelot, S. Dagdag, H. Miel, and S. Rault, “A versatile synthesis of 2‐amino‐4H‐pyrido [1,2‐a][1,3,5] triazin-4-ones from 2-aminopyridines,” Journal of Heterocyclic Chemistry, vol. 39, pp. 1061-1064, 2002.
15. Y. Hama, Y. Nobuhara, Y. Aso, T. Otsubo, and F. Ogura, “Preparation and properties of pyridine-analogue of TCNQ dianion salt,” Bulletin of the Chemical Society of Japan, vol. 61, pp. 1683-1686, 1988.
16. J. Bergman and B. Pelcman, “Synthesis of carbazoles related to carbazomycin, hyellazole and ellipticine,” Tetrahedron, vol. 44, pp. 5215-5228, 1988.