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A convenient method for the synthesis of methyl 8-oxo-3H,8H-2a,5a,7-triazaacenaphthylene-2-carboxylate by iodination of 7-allyl-4-methoxypyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester followed by elimination of hydrogen iodide has been developed. The use of 4-methoxypyrrolo[2,3-d]pyrimidine-6-carboxylic acid as the starting compound led to the formation of iodomethylpyrimido[5',4':4,5]-pyrrolo[2,1-c][1,4]oxazine, a promising precursor for the synthesis of a new tricyclic system based on pyrrolo[2,3-d]pyrimidine.

Aim. To study the interaction of 4,6-dichloropyrimidine-5-carbaldehyde with methyl- and with tert-butylglycinate depending on the reaction conditions. Results and discussion. It has been found that the reaction of 4,6-dichloro-5-formylpyrimidine with hydrochlorides of glycine esters in the presence of triethylamine leads to obtaining derivatives of N-(5-formylpyrimidin-4-yl)glycinate and cyclization products: pyrrolo[2,3-d]pyrimidine and pyrido[2,3-d]pyrimidine. Experimental part. The interaction of 4,6-dichloropyrimidine-5-carbaldehyde with methyl or tert-butyl glycinate in methanol in the presence of triethylamine depending on the molar ratio gives the mixture of 5-hydroxy-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine and 6-amino-4-chloro-7-oxopyrido[2,3-d]pyrimidine-8(7H)-yl)acetate. The composition and structure of the compounds synthesized have been confirmed by NMR-spectroscopy, chromatography mass-spectrometry and elemental analysis. Conclusions. The previously unknown derivatives of pyrrolo[2,3-d]pyrimidine and pyrido[2,3-d]pyrimidine have been obtained as a result of the interaction of 4,6-dichloro-5-formylpyrimidine with methyl and tert-butylglycinate. The reaction features depending on the reactants ratio have been studied. The prospects for the synthesis of potential biologically active compounds from 6-amino-4-chloro-7-oxopyrido[2,3-d]pyrimidine-8(7H)-yl)acetate have been described.

Aim. A search for human protein kinase CK2 inhibitors in a series of new amino-substituted pyrido[2,3-d]pyrimidine derivatives. Methods. Organic synthesis, analytical and spectral methods, molecular docking, in vitro biochemical testing. Results. Synthesis of new pyrido[2,3-d]pyrimidine derivatives with various aminogroups in positions 4 and 6 of the heterocycle was developed. Two compounds inhibiting kinase CK2 in micromolar concentrations were found among these derivatives. Conclusion. New pyrido[2,3-d]pyrimidin-7-ones containing aminogroups in positions 4 and 6 of heterocyclic system and new 4-amino-substituted pyrido[2,3-d]pyrimidin-7-amine derivatives have been synthesized. The inhibition activity of new pyrido[2,3-d]pyrimidines has been examined and the optimization modes have been suggested. Methyl-2-[(7-aminopyrido[2,3-d]pyrimidine-6-yl)amino]benzoate and N-(4-anilino-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidine-6-yl)-3,4-dimethoxy- benzamide were found to inhibit protein kinase CK2 at IC50 of 6 and 19.5 μM, respectively. Мета. Пошук нових інгібіторів протеїнкінази СК2 людини в ряду нових амінозаміщених похідних піридо[2,3-d]піримідину. Методи. Органічний синтез, аналітичні та спектральні методи, молекулярний докінг, біохімічне тестування in vitro. Результати. Розроблено методи синтезу нових похідних піридо[2,3-d]піримідину з різноманітними аміногрупами в положеннях 4, 6, 7 гетероциклу. Серед синтезованих похідних піридо[2,3-d]піримідину виявлено дві сполуки, що інгібують кіназу СК2 в мікромолярних концентраціях. Висновки. Синтезовано нові піридо[2,3-d]піримідин-7-они, що містять аміногрупи в положеннях 4, 6 гетероциклічної системи, а також 4-амінозаміщені похідні піридо[2,3-d]піримідин-7-аміну. Досліджено інгібувальну активність похідних піридо[2,3-d]піримідину та запропоновано напрями хімічної оптимізації. Встановлено, що метил 2-[(7-амінопіридо[2,3-d]піримідин-4-іл)aмінo]бензоат та N-(4-aнілінo-7-oксo-7,8-дигідропіридо [2,3-d]піримідин-6-іл)-3,4-диметоксибензамід інгібують протеїнкіназу СК2 з ІС50 6 та 19,5 μМ відповідно. Цель. Поиск новых ингибиторов протеинкиназы СК2 человека в ряде новых аминозамещенных производных пиридо[2,3-d]пиримидина. Методы. Органический синтез, аналитические и спектральные методы, молекулярный докинг, биохимическое тестирование in vitro. Результаты. Разработаны методы синтеза новых производных пиридо[2,3-d]пиримидина с различными аминогруппами в положениях 4, 6, 7 гетероцикла. Среди синтезированных производных пиридо[2,3-d]пиримидина обнаружено два соединения, ингибирующие киназу СК2 в микромолярных концентрациях. Выводы. Синтезированы новые пиридо[2,3-d]пиримидин-7-оны, содержащие аминогруппы в положениях 4, 6 гетероциклической системы, а также 4-аминозамещенные производные пиридо[2,3-d]пиримидин-7-амина. Исследована ингибирующая активность производных пиридо[2,3-d]пиримидина и предложены направления химической оптимизации. Установлено, что метил-2-[(7-аминопиридо[2,3-d]пиримидин-4-ил)амин]бензоат и N-(4-анилин-7-оксо-7,8-дигидропиридо[2,3-d]пиримидин-6-ил)-3,4-диметоксибензамид ингибируют протеинкиназу СК2 с IC50 6 и 19,5 μМ соответственно.

The reaction of 4,6-dichloropyrimidine-5-carbaldehyde with cyanomethyltriphenylphosphonium chloride gave (2Е)-3-(4,6-dichloropyrimidin-5-yl)acrylonitrile, which was further used for the preparation of 4,6-diamino-substituted pyrimidinylacrylonitrile derivatives, capable of intramolecular cyclization with the formation of new 4-amino-substituted 7-iminopyrido[2,3-d]pyrimidines. Performing the reaction with 4-amino-6-chloropyrimidine-5-carbaldehyde led to 7-amino-4-chloropyrido[2,3-d]pyrimidine, a promising intermediate for the synthesis of pyrido[2,3-d]pyrimidine-4,7-diamines.

Two variants are discussed for the synthesis of ethyl N-alkyl-N-(6-amino-5-formylpyrimidin-4-yl)-glycinate derivatives, which are converted by intramolecular cyclization under the influence of sodium methoxide to give methyl 7H-pyrrolo[2,3-d]pyrimidine-6-carboxylates. New derivatives of pyrimido- [5',4':4,5]pyrrolo[2,1-c][1,4]oxazines containing 3-chloropropyl groups at position 8 have been prepared.

The substituted vinylphosphonium salt (E)-MeSCH=C(CN)P+Ph3I− readily cyclizes under the action of benzamidine and 3-amino-s-triazole, but it does not enter cyclocondensation with 2-aminopyridine. The structure of the cyclization product with 3-amino-s-triazole was confirmed by its transformation to 7-imino-6-(triphenylphosphoranylidene)-6,7-dihydro-s-triazolo[1,5]pyrimidine which was identified by X-ray diffraction. This stabilized ylide and its analogs proved useful starting materials for regioselective syntheses of 2-R-4-alkyl-4,7-dihydro-s-triazolo[1,5-a]pyrimidin-7-ones.

The products of addition of accessible phosphorus-containing ylide Ph3 $${\mathop P\limits^+}$$ - $${\mathop C\limits^\_}$$ HCN to acyl and alkoxycarbonyl isocyanates readily cyclize under the action of methanolic HCl. This reaction was used for preparing a broad range of new 5-phosphonium derivatives of di- and trifunctionalized pyrimidine bases. Among them, the corresponding tertiary phosphonium salts containing no labile hydrogen atoms are especially important. Under mild conditions, they undergo dephosphorylation in the presence of alkalis to give 4-mercapto, 4,6-dimercapto-, and 2,4,6-trimercaptopyrimidine derivatives which are difficult or impossible to prepare by traditional routes.

12 Title compounds of type (V) are prepared and screened for their potential biological activity.