Synthesis of trans-thienyl-3-ethoxycarbonyl-2,3-dihydro[1,5]benzothiazepin-4(5H)-ones

A series of trans-thienyl-3-ethoxycarbonyl-2,3-dihydro[1,5]benzothiazepin-4(5H)-ones 6-8 was synthesized from thienylmethylidenemalonates 3a-3c and 2-aminobenzenethiol 3d in the presence of triethylamine hydrochloride at 160°. The [1,5]benzothiazepines 6-8 were alkylated using 2-dimethylaminochloroethane, 3-dimethylaminochloropropane and 3-(N-piperidino)chloropropane in order to obtain the corresponding 5-aminoalkylbenzothiazepinones 9-14 .     

Reaction of 2,3-Dihydro-1,5-benzothiazepines and Phenylacetyl Chloride in the Presence of Triethylamine： A New Aspect on the Formation Mechanism of Dihydro-1,3-oxazin-4-one Derivatives

2a,4-Disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][ 1,5]benzothiazepin-1-ones, as well as 2-substi-tuted 2,3-dihydro-3-phenylacetyl-2-styryl-benzothiazoles and 4a,6-disubstituted 3- .benzyl-4a,5-d/hydro-2-phenyl-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, were obtained from the reaction of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines with phenylacetyl chloride in the presence of triethylamine. The mechanism for the formation of 4a,5-dihydro-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, 2,3-dihydro-1,3-oxazin-4-one derivatives, was suggested.     

Reaction of dichloroketene and sulfene with N,N-disubstituted α-aminomethyleneketones. Synthesis of pyrano[2,3-e]indazole and 1,2-oxathiino[6,5-e]indazole derivatives

The polar 1,4-cycloaddition of dichloroketene to N,N-disubstituted (E)-5-aminomethylene-1,5,6,7-tetrahydro-(1-methyl)(1-phenyl)-4H-indazol-4-ones V, prepared from 1,5,6,7-tetrahydro-(1-methyl)(1-phenyl)-4H-indazol-4-ones via the 5-hydroxymethylene derivatives, gave in good yield N,N-disubstituted 4-amino-3,3-dichloro-4,5,6,7-tetrahydro-(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-(3H)ones VI, which are derivatives of the new heterocyclic system pyrano[2,3-e]indazole. Dehydrochlorination of VI with DBN afforded N,N-disubstituted 4-amino-3-chloro-6,7-dihydro(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-2(5H]-ones VII generally in satisfactory yield. Full aromatization with DDQ of VII was tried only in the case of dimethylamino derivatives, giving a moderate yield of 3-chloro-4-dimethylamino(7-methyl)(7-phenyl)pyrano[2,3-e]indazol-2(7H)-ones. Cycloaddition of sulfene to V occurred only in the case of aliphatic N-substitution to give in moderate yield 4-dialkylamino-4,5,6,7-tetrahydro-(7-methyl)(7-phenyl)-3H-1,2-oxathiino[6,5-e]indazole 2,2-dioxides, which are derivatives of the new heterocyclic system 1,2-oxathiino[6,5-e]indazole.     

Iodocyclization of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

Iodination of 2-[allyl(methallyl)sulfanyl]-6-(trifluoromethyl)pyrimidin-4(3H)-ones was accompanied by cyclization to 2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodides. 3-(Iodomethyl)-3-methyl- 7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium triiodide was reduced with sodium iodide to 3,3-dimethyl-7-oxo-5-(trifluoromethyl)-2,3-dihydro[1,3]thiazolo[3,2-a]pyrimidin-4-ium iodide.     

Cyclecondensation of 3-amino-1,2,4-triazole with substituted methyl cinnamates

The reaction of 3-amino-1,2,4-triazole ( 1 ) with substituted methyl cinnamates 2a-h leads selectively to the formation of 7-aryl-6,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones 3a-h . The structure eluci dation of the products is based on ir, ¹H and ¹³C nmr measurements and X-ray diffraction.     

A novel synthesis of methyl cis-(3-thienyl)glycidate with 2-aminothiophenol and the synthesis of [1,5]benzothiazepine derivatives

The synthesis of cis-2,3-dihydro-3-hydroxy-2-(3-thienyl)[1,5]benzothiazepin-4(5H)-one derivatives is described starting from 2-aminothiophenol and methyl cis-(3-thienyl)glycidate. The structures were confirmed by ¹H-nmr spectroscopy.     

Reactions with pyrrolidine-2,4-diones,I. New synthesis of pyrano[2,3-c]pyrrole and pyrrolo[3,4-b]pyridine systems

The synthesis of some substituted 4-hydroxy-2,5,6,7-tetrahydro-pyrano[2,3-c]pyrrole-2,5-diones (5) and 4-hydroxy-1,2,6,7-tetrahydro-5H-pyrrolo[3,4-b]pyridine-2,5-diones (6) by reacting 1,5-diaryl-pyrrolidine-2,4-diones (1) and 1,5-diaryl-1,5-dihydro-4-amino-2H-pyrrol-2-ones (3) with bis-2,4,6-trichlorophenyl malonates (4) is described.Dedicated to Prof. Dr. Dr. h. c.O. Kratky, Graz, on the occasion of his 80th birthday.     

Hydrogenation of substituted 1-arylisoquinolin-3(2H)-ones to 5, 6, 7, 8-tetrahydro- and 1, 4-dihydroisoquinolin-3(2H)-ones

Catalytic hydrogenation of variously substituted 1-arylisoquinolin-3(2H)-ones 1 gave, depending on the substituents, 5, 6, 7, 8-tetrahydroisoquinolin-3(2H)-ones ( 2 ) and/or the corresponding 1, 4-dihydro derivatives 3 . Saturation of the compounds fused with benzene ring furnished as the main products the 9, 10-dihydro- ( 4 and 5 ) and 5, 6-dihydroisoquinolin-3(2H)-ones ( 6 ) in the case of benzo[f] and benzo[h] anellation, respectively, in addition to the 1, 4-dihydro compounds detected or isolated as by-products.     

Synthesis of [1,2,4]triazoloquinazoline and [1,2,4]-triazolo-1,4-benzodiazepine derivatives

Some [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones 7 , the corresponding isomers [1,2,4]triazolo[4,3-c]quinazo-lin-5(6H)-ones and the 5-amino derivatives 8, 9 and 11 have been synthesized starting from the acylamidrazones 5 . The preparation of 5H-[1,2,4]triazolo[1,5-d]-1,4-benzodiazepin-6(7H)-ones 15 and of 5-cyclicaminomethyl-[1,2,4]triazolo[1,5-c]quinazolines 16 and 17 is also reported.     

Synthesis of some 5-Aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones from benzoxepinoisoxazolone and benzocycloheptaisoxazolone derivatives

Some 5-aryl-4,5-dihydro[1]benzoxepin-3(2H)-ones and 5-aryl-5,6,8,9-tetrahydro-7H-benzocyclohepten-7-ones were synthesized by hydrogenolytic cleavage of the isoxazole ring of 4-aryl-3-oxo-3,3a,4,10-tetrahydro[1]-benzoxepino[3,4-c]isoxazoles or 4-aryl-3-oxo-3a,4,9,10-tetrahydro-3H-benzo[4,5]cyclohepta[1,2-c]isoxazoles which in turn were prepared from ethyl 3-oxo-4-phenoxybutanoate or ethyl 3-oxo-5-phenylpentanoate by simple methods.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

Synthesis of 8,8-R,R-8,9-dihydro[1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6(7<Emphasis Type="Italic">H</Emphasis>)-ones

Three-component condensation of 3-amino-1,2,4-triazole (or its 5-methyl and 5-methylthio derivatives), dimedone (or cyclohexane-1,3-dione), and dimethylformamide dimethyl acetal afforded 8,8-R, R-8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2805–2807, December, 2005.     

Synthesis of 7H-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines and their reductive ring cleavage to 4-aminopyrrolo[2,3-d]pyrimidines

Some new 7,9-disubstituted 7H-1,2,3,4-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines 5 have been synthesized either by diazotization of 4-hydrazino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 4 obtained by hydrazinolysis of 4-chloro-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 3 or via a substitution reaction between 3 and sodium azide. 5,7-Disubstituted-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-ones 2 were obtained by cyclocondensation of 2-amino-3-cyano-1,4-disubstituted pyrroles 1 with formic acid which on chlorination using phosphorus oxychloride afforded 3 . A novel route for the synthesis of 4-amino-5,7-disubstituted-7H-pyrrolo[2,3-d]pyrimidines 6 by the reductive ring cleavage of 5 has been reported.     

A step forward in the field of drug design: 1,5-benzothiazepines and their nucleosides

(±)cis-2-(4-methoxyphenyl)-3-hydroxy/methoxy-6-methoxy/8-methoxy-2,3-dihydro-1,5-benzothiazepin-4-[5H/5-chloroacetyl/5-(4′-methylpiperazino-1′)acetyl]-ones and nucleosides viz; (±)cis-2-(4-methoxyphenyl)-3,6-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one and (±)cis-2-(4-methoxyphenyl)-3,8-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one have been synthesized by the condensation of substituted-2-aminobenzenethiols with methyl (±)trans-3-(4-methoxyphenyl)glycidate in xylene and by stirring the 3-methoxy derivative of 1,5-benzothiazepin-4(5H)-ones with sugar namely β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate at 155–160 °C in vacuo for 10 hours, respectively. The synthesized compounds have been characterized by the elemental analyses and spectral data and screened for their antimicrobial activity.     

2-Amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones. Preparation via a one-pot synthesis of 1-(ω-carboxyalkyl)-4-carbethoxy-2,3-dioxopyrrolidines

1-(ω-Carboxyalkyl)-4-carboethoxy-2,3-dioxopyrrolidines were prepared by a one-pot synthesis from β-alanine or γ-aminobutyric acid, ethyl acrylate and diethyl oxalate. In a second one-pot process these products were hydrolyzed, decarboxylated and condensed with aromatic aldehydes under the influence of hydrochloric acid to yield 1-(ω-carboxyalkyl)-4-arylidene-2,3-dioxo-pyrolidines, which yielded 2-amino-4-aryl-6-(ω-carboxyalkyl)-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)-ones upon treatment with guanidine. It was shown that 3,4-dihydro derivatives of certain 2-amino-4-aryl-5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones, formed initially in the guanidine reaction, readily undergo conversion to 5H-pyrrolo[3,4-d]pyrimidin-7-(6H)ones.     

Temperature-dependent reaction of 1,4,6-triaminopyrimidine-2(1H)-thiones with vilsmeier reagent. formation of [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones

5,7-Diamino[1,3,4]thiadiazolo[3,2-a]pyrirnidinium chloride 2 , 7-amino[1,2,4]triazolo[1,5-c]pyrimidine-5(6H)-thiones 3 and the 5(6H)-one derivative 4a were synthesized by the reaction of 1,4,6-triaminopyrimidine-2(1H)-thione 1 with phosphoryl chloride and N,N-dimethylacylamides. Further, compounds 4 were prepared from 2, 3 or 1,4,6-triaminopyrimidin-2(1H)-one 6 by the treatment with the above reagents. Compounds 3 and 4 were converted to 7-amino[1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-ones 5 .     

Pyrrole-Annulated Heterocyclic Systems. Synthesis of 2H-Pyrrolo[3,4-b][1,5]benzothiazepine 4,4-Dioxide Derivatives

Condensation of 2-nitrothiophenol with ethyl propiolate afforded 3-(2-nitrophenylthio)propenoate. Oxidation of sulfur atom to sulfone group gave ethyl 3-(2-nitrophenylsulfonyl)propenoate, which underwent condensation with tosyl methylisocyanide (TosMIC) to yield ethyl 4-(2-nitrophenylsulfonyl)pyrrole-3-carboxylate. Reduction of nitro group afforded ethyl 4-(2-aminophenylsulfonyl)-1H-pyrrole-3-carboxylate, which was cyclized to 2H-pyrrolo[3,4-b][1,5] benzothiazepin-10(9H)-one 4,4-dioxide. Similar procedure was used for the synthesis of 9,10-dihydro-10-methyl-2H-pyrrolo[3,4-b][1,5]benzothiazepine 4,4-dioxide.     

1,3-Dipolar cycloadditions of diazoalkanes to pyridazine derivatives. Thermal 1,5-sigmatropic rearrangement of methyl groups in 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazine derivatives

Thermal 1,5-sigmatropic rearrangements of one of the methyl group attached at position 3 of 3,3-dimethyl-3H-pyrazolo[3,4-d]pyridazin-4(5H)-ones 1–3 taking place either in a clock-wise or anti-clockwise direction gave N₂-methylated products 4–6 and C_3a-methylated products 7– 9 . The -7(6)-one derivative 10 and -4,7(5H,6H)-dione derivative 12 gave only N₂-methylated products 11 and 13 respectively, and 1,2-dihydro derivative 14 produced after elimination of methane, 15 .     

Synthesis of some 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones. A new heterocyclic ring system

The synthesis of the title compounds 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones 10 was effected by the Fischer indole cyclization of some 2,3-dihydro-4-phenylhydrazono[1]benzoxepin-5-ones 9 , obtained from the 3,4-dihydro-4-hydroxymethylene[1]benzoxepin-5(2H)-ones 7 by the Japp-Klingemann reaction. The structure of these new heterocyclic compounds was supported by ir, ¹H nmr and ms spectral data.     

Synthesis of 2-[mercapto(cyano)methylene]-1,2,3,4-tetrahydro-quinazolin-4-ones and 2-amino-4-methylpyrazolo-[1,5-a]quinazolin-5(4H)-one

A series of 2-[mercapto(cyano)methylene]-1,2,3,4-tetrahydroquinazolin-4-ones and 2-amino-4-methylpyrazolo[1,5-a]quinazolin-5(4H)-one were prepared from 2-cyanomethylquinazolin-4(3H)-ones via α-bromo derivatives 4 and amide oxime 8, respectively. The new compounds have been characterized by elemental analyses and ¹H-nmr, in some cases by ir and ¹³C-nmr investigations.