Synthesis of Novel Pyrrylthieno[2,3-d]Pyrimidines and Related Pyrrolo[1″,2″:1″,6″]Pyrazino[2″,3″:4,5]Thieno[2,3-d]Pyrimidines

4-Methyl-2-phenyl-5-(1-pyrryl)-6-substituted-thieno[2,3-d]pyrimidines ( 3a-c , 4a-c , 5a , b , and 6 ) have been synthesized. Some of the substituents in position 6 were used to build up different sulfur-, nitrogen- and/or oxygen-containing heterocyclic rings at that position. The 4-methyl-2-phenyl-5-(1-pyrryl)-thieno[2,3-d]pyrimidine-6-carboazide ( 20 ) was also used as a key intermediate in the synthesis of the target pyrrolo[1",2":1',6']pyrazino[2',3':4,5]thieno[2,3-d]pyrimidines.     

Synthesis and molecular structure of 4-nitro-9-phenyl-1H-and 9-hydroxy-3-oxo-9-phenyl-2,3-dihydro-9H-indeno-[2,1- c ]pyridines and 3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1- c ]isoxazolo[5,4- d ]pyridine

The 4-nitro derivatives and an oxidation by-product, 9-hydroxy-2-methyl-3-oxo-9-phenyl-2,3-dihydro-9H-indeno[2,1-c]pyridine were obtained by the nitration of N-alkyl-9-phenyl-2,3-dihydro-1H-indeno-[2,1-c]pyridines with sodium nitrite in acetic acid. Their molecular structures were studied by X-ray structural analysis. The product of [2+3] cycloaddition, 5-methyl-3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1-c]isoxazolo[5,4-d]pyridine, was obtained by the interaction of 2-chloro-1-hydroxy-2-phenylazomethine with 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1390–1399, September, 2007.     

Pyrimidines

Condensation of substituted acetophenones with arylidenebisureas at 50° C has given 2,7-di-oxo-4,5,8-triaryldecahydropyrimido[4,5-d]pyrimidines. The latter, onboiling with CF₃COOH, are converted into 2-oxo-4,5-diaryl-5H-indeno[1,2-d]pyrimidines, whose structure has been confirmed by spectral methods and by independent synthesis from 3-phenyl-1-indanone and arylidenebisureas.For part XXIII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 691–696, May, 1970.     

Structure and properties of 2,4a-dimethyl-4-phenyl-3-ethoxycarbonyl-5-oxo-4a,5-dihydro-4H-indeno[1,2-b]pyridine

The molecular and crystal structure of 2,3a-dimethyl-4-phenyl-3-ethoxycarbony-5-oxo-4a,5-dihydro-4H-indeno[1,2-b]pyridine has been determined, and its reduction and alkaline and acid hydrolysis reactions have been studied.Translated from Khimiya Geterotsiklicheskikh Soedineii, No. 10, pp. 1388–1392, October, 1984.     

Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Ionic liquid catalyzed synthesis of 7-phenyl-1,4,6,7-tetrahydro-thiazolo[5,4-d]pyrimidine-2,5-diones

A simple, green and catalyst free one pot synthesis of 7-phenyl-1,4,6,7-tetrahydro-thiazolo[5,4-d]pyrimidine-2,5-diones via a multicomponent reaction between thiazolidine-2, 4-dione (TZD), aromatic aldehyde and urea analogues is described. The ionic liquid has been used as a solvent as well as catalyst for this reaction. This reaction proceeded smoothly in good to excellent yields and offered several other advantages including short reaction time, simple experimental workup procedure and no by-products.     

Synthesis and properties of some derivatives of 2-thionoindeno [1,2-d]-pyrimidine and indeno [1,2-d] [3,1] thiazine

Derivatives of 2-thiono-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d] pyrimidine and 5-oxo-1,2,4,5-tetrahydroindeno [1,2-d] [3,1] thiazine are formed in the cyclocondensation of 2-arylideneindan-1,3-diones with thiourea and N-monomethylthiourea, while only derivatives of indeno [1,2-d]-pyrimidine are formed in the reaction with N,N-di-methylthiourea. S- and N(₃)-Alkylation occur in the alkylation of 2-thiono-4-pheny1-5-oxo-2,3,4,5-tetrahydroindeno[1,2-d]pyrimidine, while only the N-methyl derivative is formed in the alkylation of 2,5-dioxo-4-phenyl-1,2,4,5-tetrahydroindeno [1,2-d] [3,1]thiazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1136–1141, August, 1988.     

Synthesis of 8-cyano-1,4-dihydro-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylic acids as potential antimicrobial agents

The preparation of a variety of 8-cyano-1,4-dihydro-7-phenyl-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylicacids and 8-cyano-1,4-dihydro-7-p-fluorophenyl-4-oxopyrrolo[1,2-a]pyrimidine-3-carboxylic acids is described.     

Synthesis,Crystal Structure,and Spectral Study of a Novel Indenoimidazole Carboxylic Acid Amide

Russian Journal of Organic Chemistry - 3a,8a-Dihydroxy-2,8-dioxo-1,3a,8,8a-tetrahydro-2H-indeno[1,2-d]imidazole-3-carboxamide has been synthesized in 85% yield from ninhydrin and biuret via a green...     

Transformations of substituted tetrahydro-8h-indeno[1,2-d]imidazoles in concentrated sulfuric acid

The five-membered ring of the indene system in 2,8-dioxo-3a-hydroxy-8a-R-1,2,3a,8a-tetrahydro-8H-indeno[1,2-d]imidazoles is hydrolytically cleaved in concentrated sulfuric acid solutions. Depending on the reaction conditions, compounds for which substituted 4-(o-carboxyphenyl)imidazol-2-one (II), 1,8-dioxo-1,2-dihydro-8H-imidazo[4,3-a]isoindole (III), and spiro[imidazolidine-4,3′-phthalide] structures were assumed were isolated.     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

Synthesis of Derivatives of 4,6-Dioxo-1,4,6,7,8,9-hexahydropyrimido[4,5-<Emphasis Type="Italic">b</Emphasis>][1,6]naphthyridines

It has been shown that 1-aryl-8-(4-bromophenyl)-4,6-dioxo-2H(phenyl)-7-phenyl-1,4,6,7,8,9-hexahydropyrimido[4,5-b][1,6]naphthyridines are formed on heating anilides of 1-aryl-7-(4-bromostyryl)-4-oxo-1,4-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acids in PPA.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 597–600, April, 2005.     

Synthesis and herbicidal activity of novel 6-arylthio-3-methylthio-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones

A series of pyrazolo[3,4-d]pyrimidine-4-one derivatives was conveniently synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphoranes, arylisocyanate, and substituted thiophenols. The structures of the target compounds were confirmed by IR, ¹H NMR, ¹³C NMR, LC-MS, and elemental analysis. The preliminary bioassay demonstrated that some title compounds such as 6-(3-chlorophenylthio)-1-phenyl-3-methylthio-5-(4-chlorophenyl)-1H-pyrazolo[3,4-d]-pyrimidin-4(5H)-one and 6-(4-fluorophenylthio)-1-phenyl-3-methylthio-5-(3-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one showed good inhibition activities against the root of Brassica napus (rape) and Echinochloa crusgalli (barnyard grass) at a dosage of 100 mg/L.     

Synthesis of some new pyrimidine selanyl derivatives

The targeted synthesis of 2-(methylsulfanyl)-6-(furan-2-yl)-4(3H)-selenoxo -pyrimidine-5-carbonitrile failed due to the formation 1-methyl-2-methylsulfanyl-6-oxo -4-(furan-2-yl)-1,6-dihydropyrimidine-5-carbonitrile. A new series of 5,6,7,8-tetrahydro-1-benzo thieno[2,3-d]pyrimidine-4-yl substituted selanyl derivatives were prepared by the reaction of sodium diselenide with 4-chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine followed by the reaction with chloroacetic acid derivatives such as ethyl chloroacetate, chloroacetamide or chloroacetonitrile. Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine- 4-ylselanyl)acetate with hydrazine hydrate gave the corresponding hydrazino derivative. The latter reacted with ethyl acetoacetate, acetylacetone, diethyl malonate, ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate to afford 5-methyl-2-[2-(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-one, 1-(3,5-dimethylpyrazol-1-yl)-2- (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)ethanone, 1-[2-(5,6,7,8-tetrahydro -1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazolidine-3,5-dione and 5-Amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol -4-yl substituted carbonitrile or ethyl carboxylate, respectively. The structure of the novel compounds was confirmed by spectroscopic tools (IR, ¹H NMR ¹³C NMR and mass spectra) and elemental analysis.     

Pyrrolo[2,3-d] pyrimidines. I. 5-hydroxypyrrolo[2,3-d] pyrimidines

5-Hydroxy-7-alkyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitriles (VIIb-d) and 5-hydroxy-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid, ethyl ester (VIIa) were prepared from 5-carbethoxy-4-chloro-2-phenylpyrimidine (IV) via 4-[(cyanomethyl)alkylamino[-2-phenyl-5-pyrimidinecarboxylic acid, ethyl esters (Vb-d) and 4-[(carboxymethyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid, diethyl ester (Va), respectively. The hydroxy group of the pyrrolo-[2,3-d]pyrimidines could be methylated, acetylated and tosylated. Hydrolysis of 5-methoxy-7-methyl-2-phenyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbonitrile (IX) afforded the corresponding amide (X).     

Electrochemical oxidation of 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d] pyrimidine-4,6-dione (oxipurinol) at the pyrolytic graphite electrode

The electrochemical oxidation of 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d] pyrimidine-4,6-dione (oxipurinol) at the pyrolytic graphite electrode (PGE) has been studied. Oxipurinol exhibits up to three voltammetric oxidation peaks at the PGE between pH 1–12. The first pH-dependent peak (peak I_a) is proposed to be an initial, irreversible 2e-2H⁺ reaction to give 5,6-dihydro-4H-pyrazolo[3,4-d] pyrimidine-4,6-dione. This primary product further reacts by two routes. The major route, accounting for ca. 90% of the latter compound, involves a Michael addition of water followed by further electrochemical oxidation and hydrolysis to give 5,6-dihydro-5,6-dihydroxy-5-carboxy-6-diazenouracil. The minor route involves further electrochemical oxidation of 5,6-dihydro-4H-pyrazolo[3,4-d]-pyrimidine-4,6-dione in a 2e-2H⁺ reaction to give 4,5,6,7-tetrahydro-3H-pyrazolo[3,4-d]-pyrimidine-3,4,6-trione.Decomposition and, generally, additional electrochemical reactions of 5,6-dihydro-5,6-dihydroxy-5-carboxy-6-diazenouracil result in the formation of alloxan, parabanic acid, 6-diazo-isobarbituric acid and 5′-hydroxy-5-carboxy-6,6′-azouracil. The two latter compounds have never previously been reported. Decomposition of 4,5,6,7-tetrahydro-3H-pyrazolo[3,4-d]pyrimidine-3,4,6-trione results in formation of uracil-5-carboxylic acid.Detailed reaction schemes have been proposed to explain the observed electrochemistry and the formation of the observed products.     

A novel one-pot synthesis of some new interesting pyrrole derivatives

[reaction: see text] 11-(1H-Pyrrol-1-yl)-11H-indeno[1,2-b]quinoxaline and 3-(1H-pyrrol-1-yl)indolin-2-one derivatives have been synthesized in good yields in a novel, one-pot, and efficient process by condensation of 11H-indeno[1,2-b]quinoxalin-11-one or isatin derivatives with 4-hydroxyproline on solid-support montmorillonite K10 under microwave irradiation.     

Succinct and Facile Synthesis of Innovative Thiopyrimidines With Antimicrobial and Antitubercular Investigation

Abstract

To develop a series of bioactive heterocycles in minimum number of steps, 3-methyl- 4-(substituted phenyl)-1-phenyl-4,8-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5,7 (1H,6H)-dithione 2(a–j), 4-(4-substituted phenyl)-5-imino-3-methyl-1,6-diphenyl-4,5,6,8-tetrahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-7(1H)-thione 3(a–j), and N-[4-(subs- tituted phenyl)-3-methyl-1-phenyl-7-thioxo-1,4,7,8-hexahydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidine-5-yl]thiourea 4(a–j) have been synthesized from amino nitrile functionality 1(a–j). The structures of the compounds were elucidated by IR, ¹H NMR, elemental analysis, and some representative ¹³C NMR and mass spectra. All the title compounds were screened for antimicrobial and antitubercular activities, while some representative compounds were tested for antioxidant activity. Out of synthesized compounds, compounds 1j (4-CH₃), 2d (4-F), 4c (4-OH), and 4i (3-Br) exhibited maximum inhibition against Mycobacterium Tuberculosis H₃₇Rv. Compound 3c (4-OH) revealed elevated efficacy against all tested bacterial strain, while compounds 1i (3-Br), 2c (4-OH), and 3h (3-NO₂) were found efficacious against Candida albicans as compared to standard drugs.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Uncatalyzed synthesis of new substituted dihydro-2H-dipyrimido[1,2-a,4,5-d]pyrimidine-2,4(3H)-dione

Research on Chemical Intermediates - A convenient and new method has been developed for the synthesis of highly substituted dihydro-2H-dipyrimido[1,2-a,4,5-d]pyrimidine-2,4(3H)-dione derivatives by...     

Isolation of Intermediates in the Synthesis of Thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones Using Microwave Irradiation

A simple and fast method for the isolation of intermediates in the synthesis of 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones has been developed by microwave-assisted condensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryl isocyanates. The intermediates, subsequently, underwent cyclization in t-butanol in the presence of potassium t-butoxide on heating to reflux to give the desired bicyclic products, 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones.