Synthesis of 2-S-dioxo isosteres of purine and pyrimidine nucleosides. II

The preparation of glucosyl and ribosyl derivatives of 3,4,5-triamino-2H-1,2,6-thiadiazine 1,1-dioxide ( 2 ), 7-amino-4H-furazano[3,4-c]- and 7-amino-1H, 4H-imidazo[2,3-c][1,2,6]thiadiazine 5,5-dioxide ( 3 and 4 respectively) is described. Different synthetic approaches have been used.     

Pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. Sulfur dioxide analogs of pteridines

Several pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide derivatives have been synthesized for the first time by condensation of suitable 4,5-diamino-1,2,6-thiadiazine 1,1-dioxides and symmetrical 1,2-dicarbonyl compounds. Structures of these compounds have been characterized by their elementary analyses, ¹H-nmr and uv spectra as well as their pK_a values. The most striking differences between this series and the corresponding pteridines are discussed.     

Synthesis of purine-like ring systems derived from 1,2,6-thiadiazine 1,1-dioxide

7-Amino-1H,4H-imidazo[2,3-c][1,2,6]thiadiazine 5,5-dioxide was prepared by a multi-step reaction sequence form 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxide. 7-Amino-4H-furazano-[3,4-c][1,2,6]thiadiazine 5,5-dioxide was obtained by lead tetraacetate oxidation of 3,5-diamino-4-hydroxyimino-4H-1,2,6-thiadiazine 1,1-dioxide.     

Syntheses of pyrimidine and purine analogs derived from 1,2,6-thiadiazine 1,1-dioxide

5-Amino-3-oxo-2H, 4H-1,2,6-thiadiazine 1,1-dioxide and the monopotassium salt of 3,5-dioxo-2H, 4H,6H-1,2,6-thiadiazine 1,1-dioxide was obtained by condensation of sulfamide and ethyl cyanacetate and diethyl malonate, respectively. 7-Oxo-1H,4H,6H-imidazo[2,3-c]-1,2,6-thia-diazine 5,5-dioxide was prepared by a multi-step reaction sequence from 5-amino-3-oxo-2H, 4H-1,2,6-thiadiazine 1,1-dioxide.     

Synthesis of 7-amirio-2H, 4H-vic-triazolo[4,5-c]-[1,2,6]thiadiazine 5,5-dioxides

7-Amino-2H,4H-vic-triazolo[4,5-c][1,2,6]thiadiazine 5,5-dioxide was prepared by two different ways from 3,4,5-triamirio-1,2,6-lhiadiazine 1, 1-dioxide and 3,5-diamino-4H-1,2,6-thia-diazine 1, 1-dioxide respectively. 7-A:nino-2-phenyl-4H-vic-triazolo[4,5-c] [1,2,6]thiadiazine 5,5-dioxide was obtained by lead telraacetate oxidation of 3,5-diamino-4-phenylazo-1, 2, 6-thiadiazine 1, 1-dioxide.     

Reaction of 3,4,4,5-tetrachloro-4H-1,2,6-thiadiazine with benzyltriethylammonium chloride

3,4,4,5-Tetrachloro-4H-1,2,6-thiadiazine was reacted with BnEt₃NCl (10?mol%) to give perchloro-9-thia-1,5,8,10-tetraazaspiro[5.5]undeca-1,4,7,10-tetraene (up to 18% yield), 4,5,6-trichloropyrimidine-2-carbonitrile (up to 44% yield) and four minor side products: 2,7-dichlorothiazolo[5,4-d]pyrimidine-5-carbonitrile, 2-(4-chloro-6H-thiazolo[5,4-c][1,2,6]thia-diazin-6-ylidene)malononitrile, 4,8-dichloropyrrolo[2′,1′:2,3]imidazo[4,5-c][1,2,6]thiadiazine-6,7-dicarbonitrile and 4,7-dichloro-[1,2,6]thiadiazino[3,4-b]thiazolo[5,4-e][1,4]diazepin-9(10H)-one. Single crystal X-ray studies support the structures of the minor products. Tentative rationale for the formation of these minor products and the synthesis of 8-bromo-4-chloropyrrolo[2′,1′:2,3]imidazo[4,5-c][1,2,6]thiadiazine-6,7-dicarbonitrile are presented.     

A joint theoretical and experimental structural study of two novel 1,2,4-triazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]-1,3,4-thiadiazine derivatives

In this study, two novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives, 3-[2-(4-methoxyphenyl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (compound 1) and 3-[2-(3,4,5-trimethoxyphenyl)ethyl]-6-phenyl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine (compound 2), having analgesic–anti-inflammatory activity were synthesized and characterized by IR, ¹H-NMR, and mass spectroscopic techniques besides elementary analysis. Additionally, the structures and molecular packings of the mentioned compounds have been investigated by X-ray single crystal diffraction. The six-membered thiadiazine ring adopts the screw boat conformation in both the compounds. In the crystal packings of the compounds 1 and 2, C–H···N and C–H···O interactions link the molecules into a two-dimensional network and generate infinite chains. Furthermore, C–H···π intermolecular interactions provide further stability to the molecular packing in both the molecules. The conformers have been predicted by the potential energy surface scan employing the AM1 method. Geometry optimizations and electrostatic properties have been obtained using AM1 and ab initio quantum methods.     

Synthesis and intramolecular cyclization of bisthiadiazinylmethane derivatives

Bisthiadiazinylmethane derivatives obtained from 1,2,6-thiadiazine 1,1-dioxides and formaldehyde, undergo unusual intramolecular cyclizations to thiadiazino [4,3-g] [2,1,3] benzothiadiazine tetraoxides. The structures of the newly synthesized compounds are discussed on the basis of ¹H and ¹³C-NMR data and X-ray analysis.     

Furopyridines. XI. 13C NMR Spectra of 2- or 3-Substituted Furo[2,3-b]-, Furo[3,2-b]-, Furo[2,3-c]- and Furo[3,2-c]pyridine

The ¹³C nmr spectra of 2- or 3-monosubstituted furo[2,3-b]- 1a-1j , furo[3,2-b]- 2a-2j , furo[2,3-c]- 3a-3j and furo[3,2-c]pyridine derivatives 4a-4j are reported. Effects by change in annelation and substituent effects on ¹³C chemical shifts and carbon-proton coupling constants are discussed. The spectra of benzo[b]furan derivatives 5a-5j having the corresponding substituent are also reported for comparison.     

Synthese von 5,6-Dimethyl-4-oxo-1,3,4,5-tetrahydro-imidazo-[4,5-c] [1,2,6]thiadiazin-2,2-dioxid und 7-Methyl-4-oxo-1H-3,4-dihydro-pyrimido[4,5-c][1,2,6]thiadiazin-2,2-dioxid

Synthesis of 5,6-Dimethyl-4-oxo-1,3,4,5-tetrahydro-imidazo[4,5-c][1,2,6]thiadiazin 2,2-dioxide and 7-Methyl-4-oxo-1H-3,4-dihydropyrimido[4,5-c][1,2,6]thiadiazin 2,2-dioxide The derivatives of the above heterocyclic ring systems were prepared by reaction of the corresponding o-amino esters with sulfamoylchloride.     

Synthesis and reactions of some new selenolo[2,3-<Emphasis Type="Italic">c</Emphasis>]pyridazines

New series of selenolo[2,3-c]pyridazine and pyrimido[4',5':4,5]selenolo[2,3-c]pyridazine derivatives were prepared from 4-cyano-5,6-diphenylpyridazine-3(2H)-selenone. Elemental analysis, IR, ¹H NMR, and mass spectra confirmed the structures of the newly synthesized compounds.     

Studies on the synthesis of 2-(2-arylvinyl)thieno[2,3-d]pyrimidines and 5-(2-arylvinyl)triazolothieno[3,2-e]pyrimidines

Synthesis of 2-(2-arylvinyl)thienopyrimidines, by the acid catalyzed condensation of nitriles with thiophene o-aminocarbonyl compounds, the condensation of aldehydes with thiophene o-aminoamides, the base catalyzed condensation of aldehydes with 2-methylthienopyrimidines and by the Wittig condensation of 2-thieno-pyrimidinylmethylphosphonium salts with aldehydes is described. Isomeric 5-methyltriazolothienopyrimidines were found to react, under basic condition, with aldehydes yielding 5-(2-arylvinyl)triazolo[2,3-c]thieno-pyrimidines. While 5-styryltriazolo[4,3-c] isomers resisted acid catalysed isomerization, they were found to isomerize to triazolo[2,3-c]pyrimidines under base catalysis.     

Reaction of 4-thioxo-1,3-benzothiazines with thiocarbohydrazine: Synthesis and reactivity of 1,3,4-triazolo[3,2-c]quinazoline derivatives

2-Aryl-4-thioxo-1,3-benzothiazines react with thiocarbohydrazide to give the new mesoionic compounds an-hydro 1-amino-5-aryl-2-mercapto-1,3,4-triazolo[3,2-c]quinazolin-4-ium hydroxides. These compounds react with methyl iodide, aldehydes and phenacyl bromides to give 1-amino-5-aryl-2-methylthio-1,3,4-triazolo-[3,2-c]quinazolin-4-ium iodides, 4-arylidenamino-3-(o-aroylamino)phenyl-1H-1,2,4-triazolin-5-thiones and 3-(o-aroylamino)phenyl-6-aryl-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines, respectively. These latter compounds by sequential treatment with methyl trifluoromethanesulphonate and triethylamine lead to 3-(o-aroylamino)-phenyl-6-aryl-1-methyl-7-mercapto-1H-pyrazolo[5,1-c]-1,2,4-triazoles.     

Synthesis of 2-S-dioxo isosteres of purine and pyrimidine nucleosides. I. Alkyl and glycosyl derivatives of 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxide

Preparation of alkyl and glycosyl derivatives of 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxide (1) is described. Reaction of 1 with dimethyl sulfate gave the 4-methyl and 2,4-dimethyl derivatives. With benzyl chloride and allyl bromide C-4 substituted compounds were obtained. Reaction of the disilyl derivative of 1 with either 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide or 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose in the presence of Friedel-Crafts catalysts afforded the α and β anomers of the N-2 nucleoside and the β-O-glucoside. When the reaction was performed with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose, a β-C-glycoside and the α and β anomers of the N-2 nucleoside were obtained. The structure of the corresponding nucleosides were elucidated by ¹H nmr and uv by comparing the latter with those of the alkyl derivatives.     

Synthesis of derivatives of pyrazolo[1,5-a]pyrrolo[1,2-c][1,3,6]-benzotriazocine,a new class of compounds with potential CNS activity

The synthesis of derivatives of pyrazolo[1,5-a]pyrrolo[1,2-c][1,3,6]benzotriazocine was obtained by the reaction of arylaldehydes with some 1-(2-aminophenyl)-5-(pyrrol-1-yl)pyrazoles, as hydrochlorides. Characterization of this new class of compounds was effected with ir, pmr and ¹³C nmr spectral data.     

Furopyridines. X. Synthesis of tricyclic heterocycles,furo[2,3-b:4,5-c']-, furo[3,2-b:4,5-c']-, furo[2,3-c:4,5-c']- and furo[3,2-c:4,5-c']dipyridine

This paper describes the synthesis of four tricyclic heterocycles, furo[2,3–6:4,5-c']- ( 5a ), furo[3,2-b:4,5-c']- ( 5b ), furo[2,3-c:4,5-c']- ( 5c ) and furo[3,2-c:4,5-c']dipyridine ( 5d ). Starting with 2-formylfuropyridines ( 1a-d ), β-(2-furopyridyl)acrylic acids 2a-d were obtained by condensing with malonic acid. The acrylic acids were converted to the acid azides by reaction with ethyl chloroformate and the subsequent reaction with sodium azide. Heating of the acid azides at 230–240° with diphenylmethane and tributylamine gave tricyclic pyridinones 3a-d , which were converted to the respective chloro derivatives 4a-d by reaction with phosphorus oxychloride. Reduction of the chloro compounds over palladium-charcoal yielded compounds 5a-d respectively. All the compounds 2 to 5 were characterized by elemental analysis and spectral data. The H and ¹³C nmr and electronic spectral features of the furodipyridines were discussed comparing with those of the parent furopyridines.     

Regioselective N-alkylation of 1,2,6-thiadiazine 1,1-dioxide derivatives

Reactivity towards alkylating agents in relation to the capacity to bind sodium ions of 1,2,6-thiadiazine 1,1-dioxide derivatives is described. The compounds studied are: 1 , 4-nitro-, 2 , 4-cyano-, 3 ,4-ethoxycarbonyl-2H,6H-1,2,6-thiadiazin-3-one 1,1-dioxide and 4 , 3-amino-4-cyano-6H-1,2,6-thiadiazine 1,1-dioxide. Methylation with dimethyl sulfate of 4-nitro- and 4-cyanothiadiazines 1 and 2 , which show the capacity to bind sodium ions, takes place regioselectively at position 2, whilst the thiadiazines which lack this feature ( 3 and 4 ) are methylated at 2 and 6, and 6 respectively. On using diazomethane, in the absence of alkaline ions, no selectivity was observed. Glycosidation reactions of 1, 3 and 4 have also been carried out. The structure of the newly synthesized compounds are discussed on the basis of their analytical and spectroscopic data.     

Synthesis of 1H,3H-imidazo[1,5-c]thiazole-5,7-[6H,7aH]-dione and 7,8-dihydro-5-H-imidazo[1,5-c][1,3]thiazine-1,3-[2H,8aH]-dione and derivatives

1H,3H-Imidazo[1,5-c]thiazole-5,7-[6H,7aH]-dione and the corresponding 7-thione derivatives as well as 7,8-dihydro-5H-imidazo[1,5-c][1,3]thiazine-1,3-[2H,8aH]-dione and the corresponding 3-thione derivatives were synthesized starting from L -cysteine and DL -homocysteine thiolactone, respectively. The second group of bicyclic compounds represents a new heterocyclic ring system. The structures of the compounds were confirmed by spectroscopic studies and elemental analyses.     

Efficient reactions for the synthesis of pyrazolo[3,4-b]pyridine and pyrano[2,3-c]pyrazole derivatives from N-methyl-1-(methylthio)-2-nitroethen-1-amine

The efficient and novel method for the synthesis of pyrazolo[3,4-b]pyridine and pyrano[2,3-c]pyrazole derivatives from the multicomponent reaction of aromatic aldehydes (isatins), N-methyl-1-(methylthio)-2-nitroethen-1-amine, and 3-aminopyrazole or methyl 3-hydroxy-1H-pyrazole-5-carboxylate under normal laboratory conditions was reported in this research. The advantages of this research are wide range of substrates, high yields, and simple operation.     

Synthesis and structure of novel 4-arylhexahydro-1H,3H-pyrido[1,2-c]pyrimidine derivatives

A series of new 4-aryl-hexahydro-1H,3H-pyrido[1,2-c]pyrirnidine-1,3-dione derivatives 4a-k were prepared by catalytic hydrogenation of 4-aryl-1H,2H-pyrido[1,2-c]pyrirnidine-1,3-diones 3a-k. The structures of compounds were determined by ¹H and ¹³C nmr spectroscopy in solution. Steric hindrance caused twisting of the phenyl ring with respect to the pyridopyrimidine system, the effect was confirmed by X-ray diffraction.