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


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

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