Improved synthesis, spectral characteristics and spatial structure of ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate

I. V. Ukrainets, N. L. Bereznyakova, K. A. Taran, O. O. Davidenko

Abstract


The improved method for obtaining ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate being of interest as a base for synthesis of antiviral medicines has been suggested. The method involves a gradual addition of the solution of 2-amino-4-methylpyridine in triethylmethanetricarboxylate used as an acylating and condensing agent, as well as a high boiling heating agent simultaneously in the excess of triethylmethanetricarboxylate preheated to 150°C. This modification allows not only to reduce considerably regeneration of triethylmethanetricarboxylate taken in excess, but practically to avoid completely the undesirable formation of by-product – 2-hydroxy-8-methyl-N-(4-methypyridin-2-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxamide. It has been found by X-ray diffraction analysis that in the crystal the ethyl 2-hydroxy-8-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylate synthesized exists in the zwitterionic form with localization of the positive charge at the protonated nitrogen atom and the negative charge at the carbon atom in position 3 of the pyridopyrimidine ring. Based on the study of NMR 1H and 13C spectra the assumption that the test compound exits as an equilibrium mixture of two tautomeric forms in solution has been expressed.


Keywords


heterocyclic tricarbonylmethane derivatives; 2-aminopyridines; esters; 2-hydroxy-4-oxo-4H-pyrido[ 1,2-a]pyrimidine-3-carboxylic acids

References


Mane U. R., Mohanakrishnan D., Sahal D., Murumkar P. R., Giridhar R., Yadav M. R. European Journal of Medicinal Chemistry, 2014, Vol. 79, pp.422-435. Doi: 10.1016/j.ejmech.2014.04.031.

Mane U. R., Li H., Huang J., Gupta R. C., Nadkarni S. S., Giridhar R., Naik P. P., Yadav M. R. Bioorganic & Medicinal Chemistry, 2012, Vol. 29, No.21, pp.6296-6304. Doi: 10.1016/j.bmc.2012.09.008.

Mallesha L., Mohana K.N., Veeresh B., Alvala R., Mallika A. Archives of Pharmacal Research, 2012, Vol. 35, No.1, pp.51-57. Doi: 10.1007/s12272-012-0105-z.

Guo C., Linton A., Jalaie M., Kephart S., Ornelas M., Pairish M., Greasley S., Richardson P., Maegley K., Hickey M., Li J., Wu X., Ji X., Xie Z. Bioorganic & Medicinal Chemistry Letters, 2013, Vol. 23, No.11, pp.3358-3363. Doi: 10.1016/j.bmcl.2013.03.090.

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. Journal of Medicinal Chemistry, 2007, Vol. 50, No.20, pp.4917-4927.

Jin D., Takai S., Shiota N., Miyazaki M. European Journal of Pharmacology, 1998, Vol. 361, No.2-3, pp.199-205.

Donghi M., Kinzel O. D., Summa V. Bioorganic & Medicinal Chemistry Letters, 2009, Vol. 19, No.7, pp.1930-1934. Doi: 10.1016/j.bmcl.2009.02.055.

Ukrainets I. V., Bereznyakova N. L., Tugaibei I. A. Chemistry of Heterocyclic Compounds, 2008, Vol. 44, No.1, pp.50-63.

Ukrainets I. V., Taran K. A., Bereznyakova N. L. Zhurnal Organichnoi ta Farmatsevtichnoi Khimii – Journal of Organic and Pharmaceutical Chemistry, 2014, Vol. 12, No.2(46), pp.65-69.

Behbehani H., Ibrahim H. M., Makhseed S., Elnagdi M. H., Mahmoud H. European Journal of Medicinal Chemistry, 2012, Vol. 52, pp.51-65. Doi: 10.1016/j.ejmech.2012.03.004.

Krishnamurthy B., Vinaya K., Rakshith D., Prasanna D. S., Rangappa K. S. Medicinal Chemistry (Shāriqah – United Arab Emirates), 2013, Vol. 9, No.2, pp.240-248.

Calderone V., Testai L., Martelli A., La Motta C., Sartini S., Da Settimo F., Breschi M. C. The Journal of Pharmacy and Pharmacology, 2010, Vol. 62, No.1, pp.107-113. Doi: 10.1211/jpp.62.01.0012.

Roma G., Braccio M. D., Carrieri A., Grossi G., Leoncini G., Grazia Signorello M., Carotti A. Bioorganic & Medicinal Chemistry, 2003, Vol. 11, No.1, pp.123-138.

Yang Y., Shu W. M., Yu S. B., Ni F., Gao M., Wu A. X. Chemical Communications (Cambridge, England), 2013, Vol. 49, No.17, pp.1729-31. Doi: 10.1039/c3cc38131e.

Kutyrev A., Kappe T. Journal of Heterocyclic Chemistry, 1997, Vol. 34, pp.969-972.

Girreser U., Bluhm U., Clement B., Heber D. Magnetic Resonance in Chemistry: MRC, 2013, Doi: 10.1002/mrc.4005.

Zhang W. F., Xia J. H., Xu Z. H., Wang L. B., Yu C. Y. Acta Crystallographica. Section E, Structure Reports Online, 2013, Vol. 69, Pt 6, pp.o986. Doi: 10.1107/S160053681301386X.

Takechi H., Kubo K., Takahashi H., Matsumoto T. Journal of Oleo Science, 2011, Vol. 60, No.8, pp.439-443.

Zhang H., Sun Y., Chen X., Li C., Sun B. Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy, 2010, Vol. 76, No.5, pp.464-469. Doi: 10.1016/j.saa.2010.02.036.

Jasinski J. P., Butcher R. J., Hakim Al-Arique Q. N., Yathirajan H. S., Narayana B. Acta Crystallographica. Section E, Structure Reports Online, 2009, Vol. 65, Pt 8, pp.o1987-o1988. Doi: 10.1107/S1600536809027548.

Yaqub M., Shafiq Z., Qureshi A. M., Najam-Ul-Haq M. Acta Crystallographica. Section E, Structure Reports Online, 2009, Vol. 65, Pt 8, pp.o1869. Doi: 10.1107/S1600536809026373.

Jasinski J. P., Butcher R. J., Hakim Al-Arique Q. N., Yathirajan H. S., Narayana B. Acta Crystallographica. Section E, Structure Reports Online, 2009, Vol. 65, Pt 9, pp.o2201-o2202. Doi: 10.1107/S1600536809032693.

Ukrainets I. V., Gorokhova O. V., Sidorenko L. V., Bereznyakova N. L. Chemistry of Heterocyclic Compounds, 2006, Vol. 42, No.8, pp.1032-1037.

Zefirov Yu. V. Kristallographiya – Crystallography, 1997, Vol. 42, No.5, pp.936-958.

Ukrainets I. V., Bereznyakova N. L., Petyunin G. P., Tugaibei I. A., Rybakov V. B., Chernyshev V. V., Turov A. V. Chemistry of Heterocyclic Compounds, 2007, Vol. 43, No.6, pp.729-739.

Burgi H.-B., Dunitz J. D. Structure correlation. Weinheim, VCH, 1994, Vol. 2, pp.741-784.

Sheldrick G. M. Acta Crystallographica. Section A, 2008, Vol. 64, pp.112-122.


GOST Style Citations






DOI: https://doi.org/10.24959/ophcj.14.800

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)