Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 7. 7-(β-d-ribofuranosyl)-4-methylthioimidazo[4,5-d]-1,2,3-triazine

The synthesis of 7-(-D-ribofuranosyl)-4-methylthioimidazo[4,5-d]-1,2,3-triazine, 7-methyl-4-methylthioimidazo[4,5-d]-1,2,3-triazine, and 5-methyl-4-methylthioimidazo [4,5-d]-1,2,3-triazine is described. The structures of the synthesized compounds were confirmed by ¹³C NMR spectroscopy.See [1] for communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 836–838, June, 1979.     

Cyclization of 5-diazoimidazole-4-thioamide

Cyclization of 5-diazoimidazole-4-thioamide and -4-methylthioamide gives derivatives of a new heterocyclic system — imidazo[4,5-e]-2,3,4-thiadiazine — which are readily recyclized to 2-azapurines. 4-Methylthioimidazo[4,5-d]-1,2,3-triazine was synthesized, and its reactions with amines and hydrazines were studied.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

5-Diazoimidazole-4-carboxazide was isolated in the diazotization of 5(4)-aminoimidazole-4(5)-carboxhydrazide. The diazotization of N-substituted hydrazides of 5(4)-aminoimidazole-4(5)-carboxylic acis was studied. It is shown that the resulting diazo derivatives undergo cyclization to 3-arylideneaminoimidazo[4,5-d]-1,2,3-triazin-4-ones.See [1] for communication 7.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 984–985, July, 1979.     

Synthesis of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines

The corresponding 5(4)-mercaptoimidazoles, from which various 5(4)-mercaptoimidazole-4(5)-carboxylic acid derivatives were synthesized, were obtained from the amide and ethyl ester of 5-diazoimidazole-4-carboxylic acid by substitution of the diazo group. 5-Diazo-imidazole-4-hydroxamic acid does not undergo substitution with sodium disulfide but does undergo cyclization to 3-N-hydroxyimidazo[4,5-d]-1,2,3-triazin-4-one under these conditions. The kinetics of the cyclization of diazoimidazoles were studied, and the interrelationship between the structure and reactivity of the latter was examined.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1550–1554, November, 1975.     

7-(2-fluorobenzyl)-4-(substituted)-7-H-imidazo[4,5-d −1,2,3-triazines and −7H-pyrazolo[3,4-d]-1,2,3-triazines. Synthesis and anticonvulsant activity

The imidazo[4,5-d]-1,2,3-triazine and pyrazolo[3,4-d]-1,2,3-triazine analogues of the potent anticonvul-sant purine, BW 78U79 (9-(2-fluorobenzyl)-6-methylamino-9H-purine, 1 ), were synthesized and tested for anticonvulsant activity. The imidazo[4,5-d]-1,2,3-triazines 11–13 were prepared in four steps from 5-aminoimidazole-4-carboxamide (2) and the pyrazolo[3,4-d]-1,2,3-triazines 18–21 were synthesized starting with 5-amino-1-(2-fluorobenzyl)pyrazole-4-carbonitrile (14) . The intermediate 1,2,3-triazin-4-ones 6 and 16 were converted to the 4-substituted targets via the 4-(4-dimethylaminopyridinium) salts 10 and 17 . Imidazotriazine 11 had potent anticonvulsant activity against maximal electroshock-induced seizures, but its propensity to cause emesis precluded further development.     

Palladium-Catalyzed Allylic Coupling of 1,2,3-Triazolo[4,5-d]pyrimidines (8-Azapurines)

The palladium-catalyzed coupling of the sodium salt of 7-amino-1,2,3-triazolo[4,5-d]pyrimidine (8-azaadenine, 1) with allylic phosphates or carbonates resulted in mixtures of 2- and 3-substituted 1,2,3-triazolopyrimidines, which were separated by chromatography. 1-Substituted triazolopyrimidines were not isolated from these reactions. Regioselectivity (and stereoselectivity) was also observed for substitution of the allylic moiety when more than one isomer is possible from the reaction. The use of 5-amino-1,2,3-triazolo[4,5-d]pyrimidin-7-ones (8-azaguanine, 2), instead of 8-azaadenine, also resulted in mixtures. Alternate syntheses of the 3-allyl-1,2,3-triazolo[4,5-d]pyrimidines confirmed the structures of these compounds.     

Dense energetic compounds of C,H, N,and O atoms. III. 5-[4-nitro-(1,2,5)oxadiazolyl]-5H-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazole

Diazidoazofurazan 8 was obtained from the bis-diazonium salt of diaminoazofurazan 7 by treatment with sodium azide and underwent thermolysis to 5-[4-azido-(1,2,5)oxadiazolyl]-5H-[1,2,3]triazolo[4,5-c][1,2,5] oxadiazole 5 . The corresponding amine 13 was obtained from the azide 5 by reduction with stannous chloride and was oxidized by ammonium persulfate to 5-[4-nitro-(1,2,5)oxadiazolyl]-5H-[1,2,3]triazolo[4,5-c][1,2,5]oxadiazole 1 . The azide 5 was converted to a phosphinimine 9 in a reaction with triphenylphosphine.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives.

A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2- a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-ones 1b--o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b--o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)- [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.     

Iminophosphorane-mediated efficient synthesis of new tricyclic 3,5-dihydro-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones

The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with hydrazine to give selectively 6-amino-7H-1,2,3-triazolo[4,5-d]pyrimidin-7-ones 5. Compounds 5 were further transformed to iminophosphoranes 6 by reaction with triphenylphosphine, hexachloroethane and triethylamine. A tandem aza-Wittig reaction of iminophosphorane 6 with isocyanate or acyl chloride generated previously unreported 3,5-dihydro-1,2,3-triazolo[4,5-d]-1,2,4-triazolo[1,5-a]pyrimidin-9-ones 10 or 12 in satisfactory yield. X-ray structure analysis of 10 g verified the proposed structure and the reaction selectivity.     

Synthesis of pyrido[2,3-d]pyrimidine-2,4-diones from pyrimido-[4,5-e]-1,2,4-triazine-6,8-diones by reversed azadiene synthesis

It was shown that pyrimido[4,5-e]-1,2,4-triazine-6,8-diones enter the reversed azadiene synthesis reaction with ketones and vinyl ethyl ether in the presence of diethylamine or boron trifluoride etherate, and also with enamines. As a result of the reaction, pyrido[2,3-d]pyrimidine-2,4-diones are formed in good yield. Pyrimido[5,4-e]-1,2,4-triazine-5,7-diones do not undergo such reactions with acetone. The reasons for the unique behavior of the isomeric pyrimidotriazinediones in the reaction with acetone are discussed.For a preliminary communication, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 224–233, February, 1990.     

1,3-Disubstitutedpyrazole-4-caboxaldehyde in Heterocyclic Synthesis: A Novel Synthesis of Pyridine-2(1H)-thione and Fused Nitrogen and/or Sulfur Heterocyclic Derivatives

Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound 5 reacted with halogented compounds 6a–e to give 2-S-alkylpyridine derivatives 7a–e, which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives 8a–e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound reacted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and pentane-2,4-dione to give the corresponding pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine 13a,b, pyrazolo[3′,4′:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and 20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the corresponding pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.     

Diethylamine and triethylamine as sources of the dienophile component in the reverse azadiene synthesis with dimethylpyrimido[4,5-e]- and-[5,4-e]-1,2,4-triazinediones and 1,2,4,5-tetrazines

Diethylamine (DEA) and triethylamine (TEA) can function as sources for the two-carbon component in the reverse azadiene synthesis. Reaction of 5,7-dimethylpyrimido[4,5-e]-1,2,4-triazine-6,8-dione, 6,8-dimethylpyrimido-[5,4-e]-1,2,4-triazine-5,7-dione, or 1,2,4,5-tetrazine with an excess of DEA or TEA gives, respectively, the pyrido[2,3-d]pyrimidine-2,4-dione,pyrido[3,2-d]pyrimidine-2,4-dione, or pyridazine. The presence of an oxidant (atmospheric oxygen, MnO₂, or an electron-acceptor solvent) is required for the reaction to occur. Reaction of 5,7-dimethylpyrimido[4,5-e]-1,2,4-triazinedione with piperidine, morpholine, or under certain conditions DEA, results in opening of the triazine ring to give uracils with an amidine group in the 6-position.For preliminary communication, see [1, 2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1545–1558, November, 1990.     

Synthesis of certain 6-alkylthio-2,2′-anhydro-5-azauridines

β-D-Arabinofurano[1′,2′:4,5]oxazolo-s-triazin-4-one-6-thione ( 7b ) and its t-butyldimethylsilyl protected counterpart 7a were synthesized by treating the appropriate 2-amino-β-D-arabinofurano[1′,2′:4,5]-2-oxazoline with ethoxycarbonyl isothiocyanate. These 2,2′-anhydro-s-triazine nucleosides were then subjected to alkylation under similar reaction conditions. Alkylation of 3′,5′-bis(O-t-butyldimethylsilyl)-β-D-arabinofurano[1′,2′:-4,5]oxazolo-s-triazin-4-one-6-thione ( 7a ) provided the targeted S-alkylated nucleosides, i.e., the C6-SCH₃ ( 9a ), C6-SCH₂-CH = CH₂ ( 10a ), and C6-S-CH₂-C = CH ( 11a ), in reasonable yields. Attempted deprotection of these nucleosides failed. In order to circumvent this problem, 7b was alkylated with the same reagents. In each case, instead of the expected S-alkylated anhydronucleosides, a mixture of the 5-N-alkylanhydro-s-triazine-4,6-dione and 5-N-alkylanhydro-s-triazin-4-one-6-thione derivatives were obtained. The 2,2′-anhydro linkage of 7a was also found to be more stable than the s-triazine ring to mild base. Basic conditions displaced the C6-sulfur substituent and eventually caused ring opening of the s-triazine aglycone.     

Synthesis and oxidative cyclization of 3-amino-2-arylazo-5-<Emphasis Type="Italic">tert</Emphasis>-cycloalkylaminothiophenes

A series of 3-amino-4-arylazo-4,5-dihydrothiophenes has been synthesized by the reaction of arylhydrazonocyanothioacetamides (containing a tert-cycloalkylamino group) with α-halo ketones, 2-chloroacetonitrile, or 4-nitrobenzyl bromide. Their oxidation in the presence of metal acetates was investigated. It was shown that heating in pyridine with Cu(OAc)2 leads to the formation of thieno- [3,4-d]-1,2,3-triazoliumolates.     

Synthesis and Biological Activity of Pyrazolo[5,1-d] [1,2,3,5]-Tetrazine-4-ones

It is reported that benzo[1,2,3]-triazine-4-ones have widespread use, for instance, as diuretics, sedatives, tranquilizers and inflammation inhibitors and pyrazolo[1,5-a]-1,3,5-triazines are potent inhibitors of xanthine oxidase. So far,the herbicidal activities of above fused ring compounds and their analogues have not been studied. According to the principle of bioisotherism, pyrazolo[5,1-d] [1,2,3,5]-tetrazine-4-ones (2) have been developed and synthesized.     

Synthesis of some thiadiazoles, selenadiazoles and spiroheterocyclic compounds from their 2,2-dimethyl-benzopyran precursors

New series of 4,4-dimethylbenzopyrano[4,3-d]-1,2,3-selenadiazoles and 4,4-dimethylbenzopyrano-[4,3-d]-1,2,3-thiadiazoles have been synthesized from semicarbazones of chroman-4-one precursors. Some 4-acetyl-2′-acetylamino-2,2-dimethylspiro[chroman-4,5′-2-1,3,4-thiadiazolines] have been synthesized by cyclization of thiosemicarbazones of 2,2-dimethylchroman-4-ones using acetic anhydride. The selected compounds were tested for Phosphotyrosine phosphatase 1B inhibition. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 775–779, May, 2006.     

利用串联的氮杂Wittig反应方便合成3-[取代吡啶(噻唑)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮及其除草活性

用串联的氮杂Wittig关环反应合成了一系列3-[取代吡啶(嘧啶)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮.膦亚胺4和芳基异氰酸酯发生氮杂Wittig反应生成碳二亚胺5,继而在乙醇钠催化下与各种脂肪伯胺关环,以较好的收率得到目标产物7.初步生物活性测试结果表明:该系列部分化合物在100 mg/L的浓度下对双子叶植物油菜显示出较好的除草活性.     

Synthesis of new pyrrolo-[3,4-c]isoxazole, pyrrolo[2,3-d]-[1,2,3]triazole, triazolo[4,5-c]-pyridazine, and dipyrrolo-[3,2-b:3′,4′-d]pyran derivatives

New pyrrolo[3,4-c]isoxazole derivatives were synthesized from the key intermediates 4-cyanopyrrolidin-3-ones in two steps. Pyrrolo[2,3-d][1,2,3]triazoles and triazolo[4,5-c]pyridazine were obtained from 2-arylhydrazono-4-cyano-1-(4′-methoxyphenyl)-3-oxopyrrolidines by refluxing with phenylhydrazine in either ethanol or glacial acetic acid. Aldol self-condensation of 1-aryl-4-cyanopyrrolidin-3-ones afforded dipyrrolo-[3,2-b:3′, 4′-d]pyran derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1841–1848, December, 2007.     

Synthesis and properties of analogs of 5 (or 4)-aminoimidazole-4 (or 5)-carboxamide (AICA) and purines. 13. Synthesis of 5 (or 4)-hydrazinoimidazqles and their derivatives

A method for the synthesis of derivatives of 5 (or 4)-hydrazinoimidazole-4 (or 5)-carboxylic acid by reducing the corresponding diazoimidazoles with stannous chloride has been developed, and a number of hydrazones and semicarbazides have been synthesized. It has been shown that under the reduction conditions selected imidazo[4,5-d]-1, 2, 3-triazinone does not have cryptodiazonium properties.For Report 12, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1555, November, 1983.