The synthesis of new pyrrolo[2,3-d]pyrimidine-containing α-hydroxyphosphonic acids

L. V. Muzychka, I. O. Yaremchuk, O. B. Smolii, R. I. Zubatyuk, O. V. Shishkin


The work is devoted to the synthesis of new pyrrolo[2,3-d]pyrimidine-containing α-hydroxyphosphonic acids as precursors for the synthesis of potential biologically active compounds. The reaction between methyl 7-allyl-1,3dimethyl-2,4-dioxo-2,3,4,7-tetrahydro-1Н-pyrrolo[2,3-d]pyrimidine-6-carboxylate and iodine has resulted in 8-iodomethylpyrimido[5’,4’:4,5]pyrrolo[2,1-c][1,4]oxazine. The composition and structure of the compound has been confirmed by elemental analysis, NMR-spectroscopy and X-ray examination, and it is a convincing evidence of the presence of the oxazine cycle. Elimination of hydrogen halide of the iodomethyl derivative occurred with formation of 1,3,8-trimethyl-2H-pyrimido[5’,4’:4,5]pyrrolo[2,1-c][1,4]oxazine-2,4,6(1H,3H)-trione. The compound obtained upon heating with methanol in the presence of potassium carbonate was subjected to the nucleophilic attack at the carbonyl group. 7-(2-Oxopropyl)-1H-pyrrolo[2,3-d]pyrimidine derivative was formed by cleavage of the lactone ring. The treatment of ketone with diisopropyl phosphite by Abramov reaction resulted in formation of pyrimido[5’,4’:4,5] pyrrolo[2,1-c][1,4]oxazin-8-ylphosphonate, its hydrolysis was carried out by boiling in dilute hydrochloric acid. The reaction proceeded by opening of the oxazine ring, with the concomitant decarboxylation giving pyrrolo[2,3-d] pyrimidine with the 1-hydroxyphosphonoethyl substituent in position 7 of the heterocycle. The structure of the compounds obtained has been proven using NMR spectroscopy, mass-spectra and elemental analysis.


pyrrolo[2,3-d]pyrimidine; iodolactonization; Abramov reaction; α-hydroxyphosphonic acids


Flanagan M. E., Blumenkopf T. A., Brissette W. H. et al. J. Med. Chem., 2010, Vol. 53, pp.8468-8484.

Clark M. P., George K. M., Bookland R. G. et al. Bioorg. Med. Chem. Lett., 2007, Vol. 17, pp.1250-1253.

McHardy T., Caldwell J. J., Cheung K.-M. et al. J. Med. Chem., 2010, Vol. 53, pp.2239-2249.

Magee W., Evans D. Antiviral Research, 2012, Vol. 96, pp.169-180.

Valiaeva N., Wylesa D., Schooleya R., Hwub J., Beadlea J., Prichardc M., Hostetlera K. Bioorg. Med. Chem., 2011, Vol. 19, pp.4616-4625.

Kaiser M. M., Jansa P., Dracinsky M., Janeba Z. Tetrahedron, 2012, Vol. 68, pp.4003-4012.

Krecmerova M., Holy A., Andrei G. et al. J. Med. Chem., 2010, Vol. 53, pp.6825-6837.

Abdou W., Bekheit M. Arab. J. Chem., 2015, In Press.

Bankowska E., Balzarini J., Głowacka I., Wróblewski A. Monatsh. Chem., 2014, Vol. 145, pp.663-673.

Patil N., Deshmukh G., Patil S., Bholay A., Gaikwad N. Eur. J. Med. Chem., 2014, Vol. 83, pp.490-497.

Pokalwar R., Hangarge R., Maske P., Shingare M. ARKIVOC, 2006, Vol. xi, pp.196-204.

Peterson M., Corey S., Font J., Walker M., Sikorski J. Bioorg. Med. Chem. Lett., 1996, Vol. 6, pp.2853-2858.

Wang T., Wang W., Peng H., He H. J. Het. Chem., 2015, Vol. 52, pp.173-179.

Kategaonkar A., Pokalwar R., Sonar S., Gawali V., Shingate B., Shingare M. Eur. J. Med. Chem., 2010, Vol. 45, pp.1128-1132.

Zhou X., Liu Y., Chang L., Zhao J., Shang D., Liu X., Lin L., Feng X. Adv. Synth. Catal., 2009, Vol. 351, pp.2567-2572.

Smolii O. B., Muzychka L. V., Yaremchuk I. O. Zhurnal obshchey khimii, 2011, Vol. 81, pp.2207-2208.

GOST Style Citations


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

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