Synthesis and properties of some pyrimido[5,4-d]pyrimidine derivatives

A method for the preparation of 2,4,8-trioxo-6-methyl derivatives of pyrimido[5,4-d]pyrimidine with various alkyl residues in the 7 position is described. It is shown that the chlorine in the 4 position of the 2,4-dichloro derivative of pyrimido[5,4-d]pyrimidine is the most labile in nucleophilic substitution reactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 517–520, April, 1977.     

Some derivatives of pyrimido [5,4-b]quinoline

10-Chloro-2,4-dioxo derivatives of pyrimido[5,4-b]quinoline have been synthesized, and nucleophilic substitution reactions in these compounds have been studied.     

Construction of pyrimido[5,4-e]-as-triazine,purine, v-triazolo-[4,5-d]pyrimidine and pyrazolo[3,4-d]pyrimidine ring systems from 5-arylazo-6-arylidenehydrazino-1,3-dimethyluracils

Reaction of 5-arylazo-6-arylidenehydrazino-1,3-dimethyluracils (II), prepared by the treatment of 6-aryl-idenehydrazino-1,3-dimethyluracils (I) with diazotized arylamines, with dimethylformamide dimethylacetal resulted in the formation of pyrimido[5,4-e]-as-triazine (V) system, while the thermolysis of II resulted in the formation of purine (X), v-triazolo[4,5-d]pyrimidine (XII), and pyrazolo[3,4-d]pyrimidine (XIV, XIX) systems in lieu of the expected V. Reasonable mechanisms have been proposed for the formation of the various ring systems in these reactions.     

Glycolic acid-supported cobalt ferrite-catalyzed one-pot synthesis of pyrimido[4,5-b]quinoline and indenopyrido[2,3-d]pyrimidine derivatives

Herein, one-pot synthesis of pyrimido[4,5-b]quinoline and indenopyrido[2,3-d]pyrimidine derivatives was developed by the three-component reaction of aldehydes, 6-amino-1,3-dimethyluracil, and 1,3-dicarbonyl compounds in the presence of glycolic acid-supported cobalt ferrite CoFe₂O₄@SiO₂@Si (CH₂)₃NHCOOCH₂COOH as a novel magnetic catalyst in ethanol at reflux conditions. Glycolic acid-supported cobalt ferrite was characterized via Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and vibrating sample magnetometer (VSM). Moreover, the catalyst was easily recovered with magnetic separation and recycled at least for five times without significant loss of its catalytic activity. The products were formed in excellent yields over appropriate reaction times under environmentally friendly conditions. The high efficiency and easy isolation of catalyst from products with an external permanent magnet are some of the remarkable advantages of this method.     

Synthesis and properties of thiazolo[5,4-d]pyrimidine 1-oxides

Synthesis and properties of hitherto unknown thiazolo[5,4-d]pyrimidine 1-oxides are described. For example, the reaction of 6-chloro-1,3-dimethyl-5-nitrouracil (I) with methyl thioglycolate in the presence of excess triethylamine afforded 2-methoxycarbonyl-4,6-dimethylthiazolo[5,4-d]pyrimidine-5,7-(4H,6H)dione 1-oxide (IIIa), which is a versatile intermediate for the preparation of various thiazolo[5,4-d]pyrimidine derivatives.     

Synthesis of pyrazolo[3,4-d]pyrimidine derivatives using ketene dithioacetals

The cyclization of 5-amino-3-methylthiopyrazole-4-carbonitriles or 4-carboxamides 3a-j , which were prepared by the reaction of ketene dithioacetals 1a,b [1a : bis(methylthiomethylenemalononitrile; 1b : bis(methylthio)methylenecyanoacetamide] with hydrazines (hydrazine hydrate, phenylhydrazine, p-chlorophenylhydrazine, p-nitrophenylhydrazine), with formamide or carbon disulfide proceeded to give the corresponding 4-amino- or 4-hydroxy-3-methylthiopyrazolo[3,4-d]pyrimidines 6a-h in good yields. 3-Aminopyrazolo[3,4-d]pyrimidine derivatives 6i-1 were also obtained by the application of the cyclization reaction of 3,5-diaminopyrazoles with formamide.     

Nitroxyl derivatives of pyrazolo [3,4-d]pyrimidine

Conclusions Pyrazolo[3,4-d]pyrimidine nitroxyl derivatives having different distances between the paramagnetic center and the pyrazolopyrimidine ring have been prepared for the first time.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2763–2766, December, 1982.     

2-Benzazepines. 7. Synthesis of pyrimido[5,4-d][2]benzazepines

Two novel syntheses of pyrimido[5,4-d][2]benzazepines are described. The first synthesis started with 3-phenylphthalide which in three steps was converted to a functionalized pyrimidine which was cyclized to give the 2-benzazepine ring system. The second approach used o-benzoylbenzoic acid methyl ester as the starting material, which in four steps was converted to a functionalized pyrimidine which was cyclized to give a 2-benzazepine. Pyrimido[5,4-d][2]benzazepines have been found to have activity in standard central nervous system (CNS) pharmacological tests.     

Synthesis of 2-selenothieno[2,3-d]pyrimidine derivatives

Intramolecular cyclization of 2-(N-acylselenoureido)-3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thiophenes in alkaline media leads to the formation of the potassium salt (I) of 2-seleno-4-oxo-3,4,5,6,7,8-hexahydrobenzo[b]thieno[2,3-d]pyrimidine, acidification of which yielded the corresponding base in free form. Some pyrimidine compounds containing a selenium atom in the side chain were obtained by reaction of potassium salt I with halo derivatives (ClCH₂CH₂COOCH₃ and ClCH₂CH₂OH).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–754, June, 1977.     

Synthesis of 2H-pyrano[2,3-d]pyrimidine derivatives

Two series of 2H-pyrano[2,3-d]pyrimidine-2,5(6H)-dione derivatives have been prepared. Thus, the reaction of 6-hydroxy-pyrimidin-4(3H)-ones (1 a–c) with bis-2,4,6-trichlorphenyl malonates (2 a–d) or diethyl malonates (3 a–d) afforded good yields of 4-hydroxy-2H-pyrano[2,3-d]pyrimidine-2,5(6H)-diones (4 a-l). Application of our modifiedPechmann reaction^9–11 using -aminocrotonate (5) or -keto esters (6, 7) in the presence of ammonium acetate yielded the 2H-pyrano[2,3-d]pyrimidinediones8 a–h.Dedicated to Prof. Dr.Karl Schlögl, University of Vienna, on the occasion of his 60th birthday.     

5,6,7,8-四氢吡啶并[3,4-d]嘧啶衍生物的合成

以苄胺为原料,经过取代,缩合,水解,脱保护等步骤,设计合成了一系列新型的5,6,7,8-四氢吡啶并[3,4-d]嘧啶类化合物。通过1H NMR,13C NMR,MS和元素分析确证了其结构。并且对其体外抗肿瘤活性进行了研究,发现该类化合物对乳腺癌细胞MCF-7具有一定的抑制活性,其中化合物10a和10d的抑制活性达到了中效水平。     

Synthesis of new pyrido[2,3-d]pyrimidine derivatives

The mutual condensation of 4-aminouracil or 2,4-diamino-6-hydroxypyrimidine with bisacetonitrile and aldehydes was used to synthesize 2,4-dioxo-5-R-7-methyl-6-cyano-1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4,5,8-tetrahydropyrido[2,3-d]pyrimidine derivatives, which were oxidized with chromic anhydride to the corresponding 2,4-dioxo-5-R-7-inethyl-6-eyano-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine and 2-amino-4-oxo-5-R-7-methyl-6-cyano-3,4-dihydro[2,3-d]pyrimidines. The IR and UV spectra of the synthesized compounds were recorded.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 422–425, March, 1972.     

New tricyclic compounds with pyrimido[4,5-d]pyrimidine fragment, the 7,8-dihydro-1H-pyrimido[4,5,6-de]quinazoline derivatives

A reaction of 2-diaminomethylidenedimedone with aryl isocyanates leads to the formation of the corresponding ureas, which upon the action of sodium methoxide cyclize to 4-amino-7,8-dihydroquinazoline-2,5(1H,6H)-dione derivatives. The latter react with aryl isocyanates following the similar scheme to furnish 1,6-diaryl-8,8-dimethyl-7,8-dihydro-1H-pyrimido-[4,5,6-de]quinazoline-2,5(3H,6H)-diones, new tricyclic compounds containing pyrimidopyrimidine fragment.     

Synthesis of pyrimido [4,5-c] pyridazine (4-deazafervenulin), pyrazolo[3,4-d] pyrimidine and 6-(pyrazino-1-yl)pyrimidine derivatives

The synthesis of several pyrimido[4,5-c]pyridazine (4-deazafervenulin) ( 1 ), pyrazolo[3,4-d]-pyrimidine ( 2 ) and 6-(pyrazino-1-yl)pyrimidine ( 9 ) analogs has been accomplished from 6-hydrazinouracil ( 3 ). This compound could not be used as starting material for the preparation of indolo[3,2-c]pyridazino[3,4-d]pyrimidine derivatives ( 8 ) because it yielded the corresponding hydrazones ( 7 ).     

The synthesis of pyrimido[4,5-c]pyridazines and pyrimido[5,4-c]pyridazines

The Hofmann reaction on 6-methylpyridazine-3,4-dicarboxamide (1) gave a mixture of 3-methylpyrimido[4,5-c]pyridazine-5,7-dione (2), 3-methylpyrimido[5,4-c]pyridazine-6,8-dione (3) and an acid (4) of unknown structure. The Hofmann reaction on pyridazine-3,4-dicarboxamide (9) gave a mixture of pyrimido[4,5-c]pyridazine-5,7-dione ( 10 ) and an acid ( 11 ) of unknown structure. The reaction of 3-amino-6-methylpyridazine-4-carboxamide ( 18 ) with ethyl orthoformate gave 3-methylpyrimido[4,5-c]pyridazin-5-one ( 21 ). 4-Aminopyridazine-3-carboxamide ( 36 ) upon fusion with urea gave pyrimido[5,4-c]pyridazine-6,8-dione ( 37 ) while with ethyl orthoformate 36 gave pyrimido[5,4-c]pyridazin-8-one ( 38 ). Pyrimido[5,4-c]-pyridazine-8-thione ( 39 ) was obtained by the action of phosphorus pentasulfide on 38. 4-Amino-3-cyanopyridazine ( 16 ) when treated with formamide produced 8-aminopyrimido[5,4-c]-pyridazine ( 41 ). The synthesis of 4-aminopyridazine-3-carboxamide ( 36 ) and 4-amino-3-cyanopyridazine ( 16 ), both key intermediates in the synthesis of the novel pyrimido[5,4-c]pyridazine ring system was accomplished by the Reissert reaction of 4-aminopyridazine-2-oxides and subsequent conversion of the nitrile to the amide.