Synthesis of Some Pyrido[4,3- d] pyrimidine Derivatives from Malononitrile
Abstract
A series of pyrido[4,3-d]pyrimidine derivatives (5a-f) were synthesized using malononitrile (1) as a starting material. Initially 1 was bubbled by HBr in toluene for 2 hrs, which forms 4,6-Diamino-2-bromo-3-cyanopyridine (2). The compound 2 by direct hydrolysis of the nitrile group to the corresponding carboxamide by treatment of H2O2 in aqueous alkaline conditions gives4,6-Diamino-2-bromonicotinamide (3). By refluxing 3 under nitrogen with setoforthoesters, triethylorthoformate and triethyorthoacetate gives 7-Amino-5-bromopyrido[4,3-d]pyrimidin-4(3H)-one(4x) and 7-Amino-5-bromo-2-methylpyrido[4,3-d]pyrimidin-4(3H)-one(4y) respectively. Finally, by using 4x-y series,pyrido[4,3-d]pyrimidine derivatives (5a-f) were synthesized.
Keywords:
Malononitrile, Pyrido[4,3-d]pyrimidine, Orthoesters and Synthesis
References
Bennett GB, Mason RB, Alden LJ, Roach JB. 1978. Synthesis and antiinflammatory activity of trisubstituted pyrimidines and triazines. J Med Chem, 21, 623-628.
Bourguignon M, Hellal, FJ. Bihel. 2008. 6-endo-dig Cyclization of heteroarylesters to alkynes promoted by Lewis acid catalyst in the presence of Brønsted acid, Tetrahedron Lett, 49, 62–65.
Bredereck H, Simchen G, Rebsdat S, Kantlehner W, Horn P, Wahl R, Hoffman H, Grieshaber R. 1968. Products from dehydration of dicarboxylic acids derived from anthranilic acid. Chem Ber, 101, 41-50
Elnagdi MH, Elfahham HA, Ghozlan A, Elgemie GEH, Perkin Trans. 1982. Reactions with heterocyclic diazonium salts: Novel synthesis of pyrazolo[4,3-c]pyridazines, and of pyrazolo[4,3-c]pyrazoles, J Chem Soc, 1, 2667-2670.
El-Sayed NM, Eissa Amal AH, Arafa Reem KM, Ebeid MY, Soliman GA. 2003. Places and chemistry: Strasbourg—a chemical crucible seen through historical personalitie, Egyptian Journal of Pharmaceutical Sciences, 44, 207-225.
Griffin GJ, Srinivasan S, Bowman K, Calvert AH, Curtin NJ, Newell DR, Pemberton LC, Golding BT. 1998. Synthesis and Biological Properties of Quinazolinone Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase (PARP). J Med Chem, 41, 5247-5256.
Iamail AG, Wibberley DG. 1968. Pyridopyrimidines. Part IV. The preparation of pyrido[4,3-d]pyrimidines from pryano[4,3-d]pyrimidin-5-ones. J Chem Soc C, 2706-2708.
Ley SV, Thomas AW. 2003. Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation, Chem Int Ed, 42, 5400-5449.
Lornad T, Deli J, Szabo D, Foldesi A, Zschunke A. 1985. Potentially bioactive pyrimidine derivatives. III: 4-Aryl-8-arylidene-6-methyl-3, 4, 5, 6, 7, 8-hexahydropyrido [4,3-d] pyrimidine-2[1H]-ones and -2(1H)-thiones. Pharmazie, 40, 536-539.
Mascal M, Farmer SC, Arnall-Culliford JR. 2006.Synthesis of the G-C DNA Base Hybrid with a Functional Tail. J Org Chem, 71, 8146-8150.
Mi-Yeon Jang, Steven De Jonghe, Ling-JieGao and Piet Herdewijn. 2006. Regioselective cross-coupling reactions and nucleophilic aromatic substitutions on a 5, 7-dichloropyrido[4,3-d]pyrimidine scaffold, Tetrahedron Lett, 47, 8917-8920.
Mi-Yeon Jang, Steven De Jonghe, Ling-JieGao, Jef Rozenski, Piet Herdewijn. 2006. Development of Synthetic Strategies for the Construction of Pyrido[4,3-d]pyrimidine Libraries – the Discovery of a New Class of PDE-4 Inhibitors. Eur J Org Chem, 18, 4257-4269.
Schaefer H, Gewald K. 1978. Zur Synthese on 4-Aminochinolinen durch intramolekulare Friedel—Crafts-Reaktion, Monatsheftefuer Chemie, 109, 527-535.
Sonogashira K, Tohda Y, Hagihara N. 1975. Sonogashira–Hagihara reactions of halogenated glycals, Tetrahedron Lett, 16, 4467-4470.
Sorensen US, Pombo-Villar E. 2005.Synthesis of six-membered oxygenated heterocycles through carbon–oxygen bond-forming reactions, Tetrahedron, 61, 2697-2703.
Susvilo R, Palskyte ST, Brukstus A. 2005.Annulated Heterocyclo-Purines II: Fused Six-and More-Membered Heterocyclo- Purinediones-Purinones and-Purineimines, Chem Het Compounds, 41, 268-269.
Taylor EC, McKillop A, Vromen S. 1967. A simple, one-step synthesis of fused pyrimidinethiones, Tetrahedron, 23, 885-890.
Bourguignon M, Hellal, FJ. Bihel. 2008. 6-endo-dig Cyclization of heteroarylesters to alkynes promoted by Lewis acid catalyst in the presence of Brønsted acid, Tetrahedron Lett, 49, 62–65.
Bredereck H, Simchen G, Rebsdat S, Kantlehner W, Horn P, Wahl R, Hoffman H, Grieshaber R. 1968. Products from dehydration of dicarboxylic acids derived from anthranilic acid. Chem Ber, 101, 41-50
Elnagdi MH, Elfahham HA, Ghozlan A, Elgemie GEH, Perkin Trans. 1982. Reactions with heterocyclic diazonium salts: Novel synthesis of pyrazolo[4,3-c]pyridazines, and of pyrazolo[4,3-c]pyrazoles, J Chem Soc, 1, 2667-2670.
El-Sayed NM, Eissa Amal AH, Arafa Reem KM, Ebeid MY, Soliman GA. 2003. Places and chemistry: Strasbourg—a chemical crucible seen through historical personalitie, Egyptian Journal of Pharmaceutical Sciences, 44, 207-225.
Griffin GJ, Srinivasan S, Bowman K, Calvert AH, Curtin NJ, Newell DR, Pemberton LC, Golding BT. 1998. Synthesis and Biological Properties of Quinazolinone Inhibitors of the DNA Repair Enzyme Poly(ADP-ribose) Polymerase (PARP). J Med Chem, 41, 5247-5256.
Iamail AG, Wibberley DG. 1968. Pyridopyrimidines. Part IV. The preparation of pyrido[4,3-d]pyrimidines from pryano[4,3-d]pyrimidin-5-ones. J Chem Soc C, 2706-2708.
Ley SV, Thomas AW. 2003. Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and C(aryl)[bond]S bond formation, Chem Int Ed, 42, 5400-5449.
Lornad T, Deli J, Szabo D, Foldesi A, Zschunke A. 1985. Potentially bioactive pyrimidine derivatives. III: 4-Aryl-8-arylidene-6-methyl-3, 4, 5, 6, 7, 8-hexahydropyrido [4,3-d] pyrimidine-2[1H]-ones and -2(1H)-thiones. Pharmazie, 40, 536-539.
Mascal M, Farmer SC, Arnall-Culliford JR. 2006.Synthesis of the G-C DNA Base Hybrid with a Functional Tail. J Org Chem, 71, 8146-8150.
Mi-Yeon Jang, Steven De Jonghe, Ling-JieGao and Piet Herdewijn. 2006. Regioselective cross-coupling reactions and nucleophilic aromatic substitutions on a 5, 7-dichloropyrido[4,3-d]pyrimidine scaffold, Tetrahedron Lett, 47, 8917-8920.
Mi-Yeon Jang, Steven De Jonghe, Ling-JieGao, Jef Rozenski, Piet Herdewijn. 2006. Development of Synthetic Strategies for the Construction of Pyrido[4,3-d]pyrimidine Libraries – the Discovery of a New Class of PDE-4 Inhibitors. Eur J Org Chem, 18, 4257-4269.
Schaefer H, Gewald K. 1978. Zur Synthese on 4-Aminochinolinen durch intramolekulare Friedel—Crafts-Reaktion, Monatsheftefuer Chemie, 109, 527-535.
Sonogashira K, Tohda Y, Hagihara N. 1975. Sonogashira–Hagihara reactions of halogenated glycals, Tetrahedron Lett, 16, 4467-4470.
Sorensen US, Pombo-Villar E. 2005.Synthesis of six-membered oxygenated heterocycles through carbon–oxygen bond-forming reactions, Tetrahedron, 61, 2697-2703.
Susvilo R, Palskyte ST, Brukstus A. 2005.Annulated Heterocyclo-Purines II: Fused Six-and More-Membered Heterocyclo- Purinediones-Purinones and-Purineimines, Chem Het Compounds, 41, 268-269.
Taylor EC, McKillop A, Vromen S. 1967. A simple, one-step synthesis of fused pyrimidinethiones, Tetrahedron, 23, 885-890.
Statistics
123 Views | 159 Downloads
How to Cite
Teja B, R., M, S., Kumar G , A., & K, P. (2018). Synthesis of Some Pyrido[4,3- d] pyrimidine Derivatives from Malononitrile. Journal of Integral Sciences, 1(1), 19-24. Retrieved from https://jisciences.com/index.php/journal/article/view/8
Issue
Section
Research Article(s)
Copyright © Author(s) retain the copyright of this article.
