Chemistry of 1,2,3-thiadiazole. IV. Synthesis of [1]benzoxepino-[3,4-d][1,2,3]thiadiazole, [1]benzothiepino-[3,4-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d][1,2,3]thiadiazole, [1]benzoxepino[4,3-d]oxazole and [1]benzoxepino[4,3-d]oxazole. Four novel heterocycles

Starting from the readily available 4-bromomethy-5-carbethoxy 1,2,3-thiadiazole (V), 5-bromomethy-4-carbethoxy-1,2,3-thiadiazole (IX) and ethyl 2-aryl-5-bromomethyloxazole-4-carboxylate (XIV), 4,10-dihydro-10-oxo[1]benzoxepino[3,4-d][1,2,3]thiadiazole (Ia), 4,10-dihydro-10-oxo[1]benzothiepino[3,4-d][1,2,3]thiadiazole (Ib), 4,10-dihydro-4-oxo[1]benzothiepino[4,3-d] [1,2,3]thiazole (II), 2-aryl-4,10-dihydro-4-oxo[1]benzoxepino[4,3-d]oxazoles (XIXa-XIXc) and 2-aryl-4,10-dihydro-4-oxo[1]benzothiepino[4,3-d]oxazoles (XIXd-XIXf) were prepared.     

N-[3-nitro(amino)coumarin-4-yl]anthranilic acid amides. Synthesis of 6,7,8,13-tetrahydro[1]benzopyrano[4,3-b][1,4] benzodiazepine-6,8-dione

The reaction of 3-nitro-4-chlorocoumarin with anthranilic acid was used to synthesize N-(3-nitro-4-coumarinyl)-anthranilic acid, from which, through the acid chloride, we obtained a number of amides, which were reduced to N-(3-amino-4-coumarinyl)anthranilic acid amides The latter are cyclized under the influence of hydrochloric acid to 6,7,8,13-tetrahydro[1]benzopyrano-[4,3-b][1, 4]benzodiazepine-6,8-dione, which was also obtained from N-(3-amino-4-coumarinyl)anthranilic acid by its thermolysis or treatment with hydrochloric acid.See [1] for our preliminary communication.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1208–1212, September, 1989.     

Mass spectrometric investigation of some [1]benzopyrano[3,4-c]pyrazole and [1]benzopyrano[4,3-d]isoxazole derivatives

The fragmentation behaviour of some [1]benzopyrano[3,4-c]pyrazole and [1]benzopyrano[4,3-d]isoxazole derivatives under electron impact is described.     

New chromonocoumarin (=6H, 7H-[1]Benzopyrano[4,3-b][1]benzopyran-6,7-dione) derivatives from Polygala fruticosa BERG

Three chromonocoumarins ( =6H, 7H-[1]benzopyrano[4,3-b][1]benzopyran-6,7-diones) 1–3 have been isolated from the leaves and the root bark of polygala fruticosa BERG . (syn. Polygala oppositifolia L .; Polygalaceae). The structure of frutinone A ( 1 ) was established by X-ray diffraction analysis. The structures of the previously undescribed compounds frutinone B ( 2 ) and C ( 3 ) were deduced by spectroscopic methods (EI-MS, UV, IR, ¹H-and ¹³C-NMR, including NOE and COSY) in comparison with 1 . Chromonocoumarins 1–3 are the first representatives of a new type of naturally occurring compounds. Frutinone A shows strong fungicidal activity against Cladosporium cucumerinum.     

A Convenient Synthesis of NovelDerivatives of Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-dione

Summary.  Reaction of 6-Amino-2-thiouracil with hydrazonoyl halides yielded regioselectively 7-amino-1,3-disubstituted-1,2,4-triazolo[4,3-a]pyrimidine derivatives. Upon treatment with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate, the corresponding methyl (Z)-2-benzoylamino-3-([1,2, 4]triazolo[4,3-a]pyrimidin-7-yl)-amino propenoates were obtained which cyclized in the presence of sodium ethoxide to afford novel derivatives of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-(1H,8H)-diones. E-mail: mosselhi@chem-sci.cairo.eun.eg Received February 8, 2002; accepted (revised) March 18, 2002     

The synthesis and transformations of 9H-imidazo[1,2-b]pyrazolo[4,3-d]-pyridazine and 9H-pyrazolo[4,3-d]-s-triazolo[4,3-b]pyridazine derivatives

The nucleophilic and electrophilic substitutions of 6-substituted 9,9-dimethyl-9H-imidazo[1,2-b]pyrazolo- [4,3-d]pyridazines 2 , nucleophilic substitutions of 6-substituted 9,9-dimethyl-9H-pyrazolo[4,3-d]-s-triazolo- [4,3-b]pyridazines 7 and some other transformations to give compounds 3 and 8 , respectively, were studied. It was shown that both heterocyclic systems are stable under the conditions employed in these transformations.     

Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene,thieno[3,2-b]pyridine,pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).     

The vilsmeier reaction in the synthesis of 3-substituted [1]benzopyrano[4,3-b]pyridin-5-ones. An unusual pyridine ring closure

Starting from 4-chlorocoumarin-3-carbaldehyde (1) and Wittig phosphoranes 2a-d the title compounds 6a-c have been synthesized via a four-step sequence. The intermediate 4-alkylamino-3-vinylcoumarins 5a-k have been prepared by the reaction of 4-chloro-3-vinylcoumarins 3a-d with primary amines 4a-h . The coumarin derivatives 5 (except 5k ) underwent an unusual pyridine ring closure under Vilsmeier conditions to form the benzopyrano[4,3-b]pyridines 6 . When the aminoaldehydes 7 were treated with the Wittig reagent 2b the fused N-alkyl-2 (1H) -pyridinones 8 have been obtained as expected.     

Synthesis of benzo[1,2-d;3,4-d']diimidazole and 1H-pyrazolo[4,3-b]pyridine as putative A2A receptor antagonists

The synthesis and the binding affinity for the putative adenosine receptor antagonist 6-methyl-7-[1,2,3]triazol-2-yl-1,6-dihydrobenzo[1,2-d;3,4-d']diimidazole (10) and 5-oxazol-2-yl-1H-pyrazolo[4,3-b]pyridin-3-ylamine (16) are reported. The title compounds were prepared from commercially available 1-chloro-2,4-dinitrobenzene (1) and 2-chloro-6-methoxy-3nitropyridine (11), respectively, but proved devoid of affinity for the adenosine A1 and A2A receptors.     

Synthesis of thieno[2,3-d]thia[1]pyrano[4,3-b]pyrrole derivatives

It is shown that 2-methyl-3-carbethoxy-4H,8H,5,6-dihydrothieno[2,3-d]thia[1]pyrano [4,3-b]pyrrole and 8-methyl-9-carbethoxy-10H,5,6-dihydrothieno[2,3-d]thia[1]chromeno[4,3-b]pyrrole and their S,S-dioxides, respectively, are obtained in the reaction of 2-methyl-3-carbethoxy-4-thienylhydrazine with tetrahydro-4-thiopyrone, tetrahydro-4-thiopyrone S, S-dioxide, 4-thiochromanone, and 4-thiochromanone S,S-dioxide in the presence of an acid catalyst.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 195–196, February, 1979.     

6,6-Heptamethylenetetrahydropyran-2,4-dione in the Synthesis of Benzo[f]pyrano[3,4-b]quinolines and Pyrano[4,3-b][4,7]phenanthrolines

Three-component condensation of 6,6-heptamethylenetetrahydropyran-2,4-dione with 2-amino-naphthalene or 6-aminoquinoline and aromatic aldehydes in an aliphatic alcohol afforded 12-aryl-9,9-hepta-methylene-8,9,10,12-tetrahydro-7H-benzo[f]pyrano[3,4-b]quinolin-11-ones and 12-aryl-9,9-heptamethylene-8,9,10,12-tetrahydro-7H-pyrano[4,3-b][4,7]phenanthrolin-11-ones, new N,O-heterocycles which include azaor diazaphenanthrene system fused to -pyrone ring and aromatic and spiro substituents.     

Synthesis of 5H-[1]benzopyrano[4,3-b]pyridin-5-ones containing an azacannabinoidal structure

Starting from 7-alkoxy-4-aminocoumarins 5,6,8,12 , and 13 as key intermediates, this paper describes two different methods for the preparation of azacannabinoidal 5H[1]benzopyrano[4,3-b]pyridin-5-ones 24–27, 38 , and 39 containing typical structural requirements for ZNS activity. First, Michael addition of 6 and 8 to the double bonds of alkyl vinyl ketones 14 and 15 resulted in a mixture of tetrahydropyridines 24–27 and fused pyridines 20–23 the latter of which were reduced by sodium cyanoborohydride to give the target compounds 24–27 . The second, pyridine ring closure was accomplished by a combination of Vilsmeier acetylation and formylation resulting in fused 4-chloropyridines 31–33 followed by reduction.     

1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine and its derivatives

The synthesis of the parent ring system and some of the derivatives of 1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine are described.     

Synthesis of methyl(ethyl) pyrazolo[4,3-b]pyridine-6-carboxylates and their conversion to tert-butyl 4,5,6,7-tetrahydropyrazolo-[4,3-b]pyridine-6-carboxylates

Chemistry of Heterocyclic Compounds - N-Boc-4-aminopyrazole-5-carbaldehydes react with methyl 3,3-dimethoxypropanoate or β-keto esters in acetic acid under reflux to form methyl(ethyl)...     

1,2,3-Triazolo[4,5-d]-1,2,4-triazolo[4,3-b]pyridazines

Some new 1,2,3-triazolo[4,5-d]-1,2,4-triazolo[4,3-b]pyridazines were prepared starting from the corresponding 1,2,3-triazolo[4,5-d]pyridazines via the formation of the 1,2,4-triazole ring, by condensation of an appropriate monocarbon fragment with the 4-hydrazino substituent and the nitrogen atom in the 5 position of the heterocycle. Condensation of 4-phenylhydrazino substituted derivatives with formic acid gave zwitterionic compounds.