Abstract
Reactivity of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carbaldehyde (I) towards N- and C-nucleophiles was described. A series of new enaminones II–III, Schiff’s base IV, and hydrazinomethylenediketones V–VIII and X were prepared in good yields. Cyclization of compounds X was achieved by an action of acetic acid to give pyrazolo[3,4-d]pyrido[1,2-a]pyrimidines XI. Base catalyzed Knoevenagel condensation of aldehyde I with some active methyl and methylene compounds led to a series of chalcone-like derivatives XII, XV, XVII, XX, XXIII, XXV, XXVII, XXIX, XXXI, XXXII, and XXXV, in fair yields. Cyclization of enones XII, XV, and XX with hydrazine gave novel heterocyclyl substituted pyrazoles XIII, XVII, and XXI, respectively. Pyrano[2,3-d]pyrido[1,2-a]pyrimidine-2,5-diones XXXIII, XXXIV, and XXXVI derivatives were obtained via cyclization of their respective enone derivatives.
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References
Abass, M. (2000). Chemistry of substituted quinolinones. Part II. Synthesis of novel 4-pyrazolylquinolinone derivatives. Synthetic Communications, 30, 2735–2757. DOI: 10.1080/00397910008086898.
Abass, M., & Ismail, M. M. (2000). Chemistry of substituted quinolinones I. Synthesis of novel triazinylmethylquinolinone derivatives. Chemical Papers, 54, 187–195.
Abass, M., & Othman, E. S. (2001). Chemistry of substituted quinolinones. III. Synthesis and reactions of some novel 3-pyrazolyl-2-quinolinones. Synthetic Communications, 31, 3361–3376. DOI: 10.1081/SCC-100106047.
Belicová, A., Seman, M., Milata, V., Ilavsky, D., & Ebringer, L. (1997). Biological activity of new aza analogues of quinolones. Folia Microbiologica, 42, 193–198. DOI: 10.1007/BF02818977.
Dominguez, J., Charris, J., Iarrusso, L., Lopez, S., Lobo, G., & Riggione, F. (1996). Synthesis of pyridopyrimidone derivatives and their activity against P. falciparum in vitro. Il Farmaco, 51, 781–784.
Ferrarini, P. L., Mori, C., Armani, G., & Rossi, L. (1995). Synthesis of some 4H-pyrido[1,2-a]pyrimidin-4-ones as antimicrobial agents. Il Farmaco, 50, 69–72.
Hermecz, I., & Mészáros, Z. (1988). Pyrido[1,2-a]pyrimidines; New chemical entities in medicinal chemistry. Medicinal Research Reviews, 8, 203–230. DOI: 10.1002/med.2610080204.
Ibrahim, S. S., Abdel-Halim, A. M., Ismail, M. M., & Othman, E. S. (1994). Synthesis of some heterocyclic rings as substituents to quinolone moiety. Indian Journal of Heterocyclic Chemistry, 4, 125–130.
Ingalls, E. A., & Popp, F. D. (1967). The preparation, structure and reactions of some “malonyl-α-aminopyridines”. Journal of Heterocyclic Chemistry, 4, 523–526. DOI: 10.1002/jhet.5570040411.
Ismail, M. M., Abdel-Halim, A., & Abass, M. (1997). Quinolones substituted by different moieties. Part 2. Reactions of 1,2-dihydro-4-hydroxy-1-methyl-2-oxoquinoline-3-carbaldehyde with acyclic active methylene compounds. Journal of the Serbian Chemical Society, 62, 977–986.
Janssen, C. G. M., Knaeps, A. G., Kennis, L. E. J., & Vandenberk, J. (1990). Novel 3-piperidinyl-1,2-benzisoxazoles. European Patent Application No. EP0368388. Munich, Germany: Europen Patent Office.
Kappe, T., Aigner, R., Jöbstl, M., Hohengassner, P., & Stadlbauer, W. (1995). Reactions of 3-acyl-4-hydroxy-2(1H)-quinolones with nitrogen bases. Heterocyclic Communications, 1, 341–352.
Kapui, Z., Varga, M., Urban-Szabó, K., Mikus, E., Szabó, T., Szeredi, J., Bátori, S., Finance, O., & Arányi, P. (2003). Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol -3(2H)-one-1,1-dioxide (SSR69071), a novel, orally active elastase inhibitor. Journal of Pharmacology and Experimental Therapeutics, 305, 451–459. DOI: 10.1124/jpet.102.044263.
Kepe, V., Kocevar, M., & Polanc, S. (1996). One-pot synthesis of some 2H-pyran-2-one derivatives. Journal of Heterocyclic Chemistry, 33, 1707–1710. DOI: 10.1002/jhet.5570330626.
La Motta, C., Sartini, S., Mugnaini, L., Simorini, F., Taliani, S., Salerno, S., Marini, A. M., Da Settimo, F., Lavecchia, A., Novellino, E., Cantore, M., Failli, P., & Ciuffi, M. (2007). Pyrido[1,2-a]pyrimidin-4-one derivatives as a novel class of selective aldose reductase inhibitors exhibiting antioxidant activity. Journal of Medicinal Chemistry, 50, 4917–4927. DOI: 10.1021/jm070398a.
Matsuishi, N., Amano, M., Nakagawa, Y., Kakehi, N., Kawashima, T., & Omura, S. (1987). Pyrido[1,2-a]pyrimidine derivatives. European Patent Application No. EP0242230. Munich, Germany: Europen Patent Office.
Matsutani, S., Mizushima, Y., & Doteuchi, M. (1987). 9-(Substituted thio)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, their manufacture and use. European Patent Application No. EP0218423. Munich, Germany: Europen Patent Office.
O’Mahony, M. J., West, P. J., Lindell, S. D., & Macritchie, J. A. (1997). Fungicidal pyridopyrimidines. British Patent No. GB2307177. Newport, South Wales, UK: British Patent Office.
Zacharias, G., Wolfbeis, O. S., & Junek, H. (1974). Über Anilinomethylenverbindungen der Cyclohexandione. Monatshefte für Chemie, 105, 1283–1291. DOI: 10.1007/BF00909865.
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Abass, M., Ismail, M.M., Abdel-Monem, W.R. et al. Substituted pyridopyrimidinones. Part 5. Behavior of 2-hydroxy-4-oxo-4H-pyrido[1,2-α]pyrimidine-3-carbaldehyde in nucleophilic condensation reactions. Chem. Pap. 64, 72–83 (2010). https://doi.org/10.2478/s11696-009-0100-0
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DOI: https://doi.org/10.2478/s11696-009-0100-0