Synthesis of 4,10-dihydro-4,10-dioxo-1H[1]benzothiopyrano[3,2-B]pyridine and 7-oxo-7,13-dihydro[1]benzothiopyrano[2,3-b]-1,5-benzodiazepine

3-Amino-4H-1-benzothiopyran-4-one (3-aminothiochromone) was easily prepared by reaction of 3-bromo-thiochromen-4-one with sodium azide in methanol-water. Condensation of 3-aminothiochromone with diethyl ethoxymethylenemalonate and with dimethyl acetylenedicarboxylate gave intermediates, which were thermally cyclized to give 4,10-dihydro-4,10-dioxo-1H[1]benzothiopyrano[3,2-b]pyridinecarboxylates. 3-Formyl-thiochromone was condensed with o-phenylenediamine to give 7-oxo-7,13-dihydro[1]benzothiopyrano[2,3-b]-1,5-benzodiazepine.     

The synthesis of 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles,11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles and 1,2,4-triazolo[3,4-f]-1,2,4-triazino[4,5-a]indoles

This paper describes the synthesis of the previously unknown 11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles (2) and 11H-tetrazolo[4,5-b]pyridazino[4,5-b]indoles (3) from 4-hydrazino-5H-pyridazino[4,5-b]indoles (1) , as well as the synthesis of 1,2,4-triazolo[3,4-f]-1,2,4-triazino-[4,5-a]indoles (10) from 2-indolecarbohydrazide (4) . Compounds 2 were obtained by acylation of compounds 1 , followed of thermal cyclization and compounds 3 by treating compounds 1 with nitrous acid. The reactions of compound 4 with formic acid or ethyl orthoformiate gave 1,2-dihydro-1-oxo-1,2,4-triazino[4,5-a]indole (6) . Treating this last compound with phosphorus oxychloride or phosphorus pentasulfide, followed by hydrazine, gave 1-hydrazino-1,2,4-triazino-[4,5-a]indole (9) . Acylation of this last compound, followed of cyclization gave compounds 10 . All the compounds were characterized by elemental analysis and ir and ¹H-nmr spectra.     

Hydrazinolysis of 4-acyl and 4-ethoxycarbonyl-3H-imidazo[1,5-b]-pyridazine-5,7-(6H)diones: 8-Oxo-1,4,7,8-tetrahydropyridazino-[4,5-c]pyridazine, 8-oxo-7,8-dihydropyridazino[4,5-c]pyridazine and 5,8-dioxo-1,4,5,6,7,8-hexahydropyridazino[4,5-c]pyridazine derivatives

Reaction of 4-acyl-3H-imidazo[1,5-b]pyridazine-5,7-(6H)diones with hydrazine hydrate gave 3R-5R′-8-oxo-1,4,7,8-tetrahydropyridazino[4,5-c]pyridazine together with 3R-5R′-8-oxo-7,8-dihydropyridazino[4,5-c]pyridazine derivatives. Their structures were assigned by means of elemental analyses and spectroscopic data (ir, uv, nmr and ms). The conclusive structural elucidation involved the fact that 2R-4-ethoxycarbonyl-3H-imidazo[1,5-b]pyridazine-5,7-(6H)-diones treated with hydrazine hydrate afforded 3R-5,8-dioxo-1,4,5,6,7,8-hexahydropyridazino-[4,5-c]pyridazine which, upon dehydrogenation, gave products previously reported in the literature.     

Synthesis of 1-hydrazinopyridazino[4,5-b]quinoxaline and related compounds

This paper describes the synthesis of 1-hydrazinopyridazino[4,5-b]quinoxaline ( 10 ), tetrazolo[4,3-b]pyridazino[4,5-b]quinoxaline ( 11 ) and some 1,2,4-triazolo[4,3-b]pyridazino[4,5-b]quinoxalines 13 . Starting with 2-ethoxycarbonyl-3-methylquinoxaline 1,4-dioxide ( 1 ), 1,2-dihydro-1-oxopyridazino[4,5-b]quinoxaline ( 5 ) was prepared by three different ways: (a) chlorination of 1 in acetic acid gave 2-ethoxycarbonyl-3-dichloromethylquinoxaline 1,4-dioxide, which reacts with an excess of hydrazine to give about 60% of 5 ; (b) oxidation of 1 with selenium dioxide gave 90% of 2-ethoxycarbonyl-3-formylquinoxaline 1,4-dioxide ( 3 ), which reacts with hydrazine to give 5 (63%); (c) compound 3 was treated with hydrazine to give 1,2-dihydro-1-oxopyridazino-[4,5-b]quinoxaline 1,4-dioxide ( 4 ) (70%), which by reduction with sodium dithionite gave 5 (80%). Compound 5 reacts with phosphorus pentasulfide or the Lawesson reagent to give 1,2-dihydro-1-thiocarbonylpyridazino[4,5-b]quinoxaline ( 9 ), which treated with hydrazine gave 5 (80%). This last compound reacts with nitrous acid to give 11 . Some hydrazones 12 from 10 are described. Heating the aldehyde hydrazones 12a,c,d with dimethylsulfoxide some 1,2,4-triazolo[4,3-b]pyridazino[4,5-b]quinoxalines 13 were obtained. Compound 13a was also obtained in the reaction of 10 with benzoyl chloride. Reaction of 3 with phenylhydrazine gave 1,2-dihydro-1-oxo-2-phenylpyridazino[4,5-b]quinoxaline ( 6 ). Reactions of 5 with acetic anhydride and dimethylsulfate gave, respectively, 1-acetoxypyridazino[4,5-b]quinoxaline ( 8 ) and 1,2-dihydro-1-oxo-2-methylpyridazino-[4,5-b]quinoxaline ( 7 ). All the compounds were characterized by elemental analysis and ¹H-nmr spectra. Compounds 5 and 10 showed antihypertensive activity in rats.     

Five-membered 2,3-dioxo heterocycles: LXXX. Recyclization of 1H-pyrrole-2,3-diones into pyrazolo[1,5-a]pyrimidines by the action of pyrazolamine. Crystalline and molecular structure of substituted pyrazolo[1,5-a]pyrimidine

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-methyl-4-phenyl-1H-pyrazol-5-amine to give methyl 7-arylcarbamoyl-6-aroyl-2-methyl-3-phenylpyrazolo[1,5-a]-pyrimidine-5-carboxylates. The molecular and crystalline structures of methyl 6-benzoyl-7-(4-chlorophenylcarbamoyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylate were studied by X-ray analysis.     

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 some new derivatives of 4-hydrazino-5H-pyridazino[4,5-b]indole

This paper describes the synthesis of 1-chloro-4-hydrazino-5H-pyridazino[4,5-b]indole ( 4 ) and some of the triazoles ( 6–8 ), tetrazoles ( 10–11 ), triazolotetrazoles ( 9 ) and bis-tetrazoles ( 12 ) derived from it. All of these were previously unknown compounds. Treating 1,4-dioxo-1,2,3,4-tetrahydro-5H-pyridazino[4,5-b]indole ( 1 ) with phosphorus oxychloride gave 1,4-dichloro-5H-pyridazino[4,5-b]indole ( 2 ), which reacts regioselectively with hydrazine to give compound 4 . The reactions of 4 with formic and acetic acids gave 6-chloro-11 H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]indoles ( 6a-6b ), respectively. Reaction of compound 6a with hydrazine gave 6-hydrazino-11H-1,2,4-triazolo[4,3–6]-pyridazino[4,5,-b]indole ( 8 ). This with nitrous acid gave 6-azido-11H-1,2,4-triazolo[4,3-b]pyridazino[4,5-b]-indole ( 9 ). Compound 4 reacted with nitrous acid to give 6-chloro-11H-tetrazolo[4,5-b]pyridazino[4,5-b]-indole ( 10 ), which gave 1,4-diazydo-5H-pyridazino[4,5-b]indole ( 12 ), through successive reactions with hydrazine and nitrous acid. All compounds were characterized by elemental analysis, ir and ¹H-nmr spectra.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene. 4. Synthesis of 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines

Thirteen 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines 11 have been synthesized in three steps from 4-amino-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene ( 6 ), which was obtained from the reduction of either 4-azido 4 or 4-hydroxyimino 5 derivatives. All the compounds have been evaluated as potential antidepressive agents.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

The photochemical synthesis of novel heterocyclic compounds from s-triazolo [4,3-b] pyridazine,III

s-Triazolo[4,3-b]pyridazine (I) reacted photochemieally with bieyélo[2.2.1] hepla-2,5-diene, 1,5-cyclooctadiene, 1,3-cyclooctadiene, methylene cyclohexane, diethyl cis-1,2,3,6-tetrahydro-phthalate and ethyl 2-cyclopentene-1-acetate to givt: the following products: the endo and exo isomers of 4a, 5, 8a, 9-tetrahydro-9-rnethylene-5,8-rnethano-8H-s-triuzolo[1, 5-a]indole (II) and the endo and exo-9-cyanometliyl products (III and IV) from bicyclo[2.2.1] hepta-2,5-diene; 4a,5,-9, 10, 10a, 11-huxahydro-11-methylene-6H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole (V) and the 11-cyanomethyl product VI from 1,5-cyclooctadiene: 4a,7,8,9,10,10a-hexahydro-11 -inethylene-11H-cycloocta[4,5]pyrrolo[1,2-b]-s-triazole(VII),4a, 5, 7, 8, 10a, 11-hexahydro-11-methylene-6H-cycloocta[4,5]pyrroIo[1,2-b]-s-triazole (VIII) and their respective 9-cyanomethyl products (X and 1X) from 1,3-cyclooctadiene; 6′, 7′ -dihydro-7′ -methylenespiro[cyclohexane-1, 5′-[5H] pyr-rolo[1,2-b]-s-triazole] (XI), 6′, 7′-dihydro-7′-meth) lene. spiro cyclohexane-1, 6′-[5H]pyrrolo[1,2-b]-s-triazole] (XII) and their respective 7 -eyanomethyl products (XIII and XIV) from melhylene cyclohexane; 6,7-dicarbethoxy-9-cyanomelhyl-4a, 5, 7, 8, 8a, 9-hexahydro-6H-s-triazolo[1,5-a]indole (XV) from diethyl cis-1, 2, 3, 6-tetrahydrophlhalate: and 5-earl)elhoxymethyl-8-eyanomethyl-4a, 5, 6, 7, 7a, 8-hexahydrocyclopenta[4,5]pyrrolo( 1, 2-b]-s-triazole (XVI) from ethyl 2, 2-cyclo-pentene-1-acetate. Many other alkenes, particularly the phenyl ethylenes, did not react with compound 1. In general, more than one product was isolated for each reaction except in the case of the two ester alkenes where a single eyanomethyl product was observed.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.     

Synthesis of pyrimidino[4,5-b][1,5]benzodiazepin-2-ones and pyrimidino[1,6-a]benzimidazol-1-ones from 4-ethoxycarbonylamino-1H-1,5-benzodiazpine-3-carbonitrile via 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles

Reactions of 4-ethoxycarbonylamino-1H-1,5-benzodiazepine-3-carbonitrile (2) with aliphatic primary amines gave 1-substituted 4-(2-aminoanilino)pyrimidin-2(1H)-one-5-carbonitriles 3. Analogous reactions of 2 with aromatic primary amines afforded 2-(2′-anilino-1′-cyanovinyl)benzimidazoles 5 and 6. Upon treatment with triethylamine, 3 underwent intramolecular cyclization to give 3-substituted 5-aminopyrimidino[4,5-b]-[1,5]benzodiazepin-2(3H,11H)-ones 8 . Heating of 3 with p-toluenesulfonic acid in ethanol gave 2-substituted pyrimidino[1,6-a]benzimidazol-1(2H)one-4-carbonitriles 9 . Reactions of 2 with hydrazines were also described. Mechanistic pathways are proposed to account for the products.     

Synthesis of quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts

The reaction of dihydroimidazole-2-thiol with N-(3-chloro-2-oxopropyl)phthalimide gave 2-[3-(4,5-dihydroimidazol-2-ylsulfanyl)-2-oxopropyl]-1,3-dioxo-1H-isoindole which underwent intramolecular heterocyclization to dihydroimidazothiazole system by the action of a dehydrating agent. Treatment of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with concentrated hydrochloric acid led to the formation of dihydroimidazo[2,1-b]thiazol-3-ylmethanamine. Water-soluble quaternary 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazolium salts were obtained by alkylation of 3-(1,3-dioxo-1H-isoindol-2-ylmethyl)-5,6-dihydroimidazo[2,1-b]thiazole with alkyl halides.     

Synthesis of new thiazolo[2,3-b]pyrimidine derivatives of pharmaceutical interest

2H-5-Amino-6-cyano-3,7-dioxothiazolo[2,3-b]pyrimidine was subjected to ring formation affording thiazolo[2,3-b]pyrimidine derivatives. 2H-5-Amino-6-cyano-3,7-dioxo-2-phenylmethylenethiazolo[2,3-b]pyrimidine was also subjected to ring formation affording pyrimido[4,5-d]-, pyrano[2,3-d]-, and pyrido[2,3-d]thiazolo[2,3-b]pyrimidine derivatives. 2-Anilinothiocarbonyl-3,9-dioxo-8-imino-7-phenyl-6-thioxothiazolo[2,3-b]pyrimido[4,5-d]pyrimidine and 8-amino-3,9-dioxo-6-thioxothiazolo[2,3-b]pyrimido[4,5-d]pyrimidine reacted with α-haloactive-methylene compounds to afford heterocyclic compounds containing two, fused and isolated, thiazole moieties, respectively.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are described.     

Synthesis of 5,8-dihydro-5-oxo-2-(3- or 4-pyridinyl)-pyrido[2,3-d]pyrimidine-6-carboxylic acids and the reinvestigation of the thermal cyclization of diethyl (2-hydroxy-4-pyrimidinyl)amino-methylenemalonate

Diethyl [2-(3- or 4-pyridinyl)-4-pyrimidinyl]aminomethylenemalonates 5 prepared by the reaction between 2-(3- or 4-pyridinyl)-4-pyrimidinamines 3 and diethyl ethoxymethylenemalonate ( 4 ) were thermally cyclized to afford ethyl 5,8-dihydro-5-oxo-2-(3- or 4-pyridinyl)pyrido[2,3-d]pyrimidine-6-carboxylates 6 . The later were alkylated with ethyl iodide and then saponified to give 5,8-dihydro-8-ethyl-5-oxo-2-(3- or 4-pyridinyl)pyrido-[2,3-d]pyrimidine-6-carboxylic acids 2 . Thermal cyclization of diethyl (2-hydroxy-4-pyrimidinyl)amino-methylenemalonate ( 8 ) gave ethyl 1,6-dihydro-4,6-dioxo-4H-pyrimido[1,6-a]pyrimidine-3-carboxylate ( 10 ) instead of ethyl 5,8-dihydro-2-hydroxy-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate ( 9 ) as previously claimed.     

Die molekulare und kristalline Struktur von 9,10-Dihydro-4-(3-dimethylamino-propyliden)-4H-benzo[4,5] cyclohepta[1,2-b]thiophen-hydrochlorid. Untersuchungen über synthetishe Arzneimittel, 19. Mitteilung [1]

The α-isomer of 9,10-dihydro-4-(3-dimethylamino-propylidene)-4 H-benzo[4,5] cyclohepta [1, 2-b] thiophen is shown to have the trans configuration by means of an X-ray analysis of its hydrochloride.     

Synthesis and properties of 2-substituted 1-aryl-7,8-dihydro-6H-pyrimido[4,5-b]pyrindine-4-ones

In reaction with acylating agents, 2-aryl-2-methyl-7,8-dihydro-6H-pyrimido[4,5-b]pyrindin-4-ones are acylated at the methyl group and also enter into reaction with diethyl oxalate. 1-Aryl-2-phenacyl-7,8-dihydro-6H-pyrimido[4,5-b]pyrindin-4-ones undergo dehydration under the influence of concentrated sulfuric acid. On the basis of the PMR and UV spectra, it was concluded that 1-aryl-2-acetonyl(phenacyl)-7,8-dihydro-6H-pyrimido[4,5-b]pyrindin-4-ones exist in two tautomeric forms with strong intramolecular hydrogen bonds of the chelate type — enaminocarbonyl and enol.     

The synthesis of some 4H-pyrimido[2,1-b]benzothiazol-4-ones

A series of 8-substituted and 7,8-disubstituted-4-oxo-3-(4H-pyrimido[2,1-b]benzothiazole)carboxylic acids and esters including a 9-aza analog were synthesized from substituted 2-aminobenzothiazoles and diethyl ethoxymethylenemalonate. The 9-aza analog, ethyl 8-methoxy-4-oxo-3-(4H-pyrido[3′,2′:4,5]thiazolo[3,2-a]pyrimidine)carboxylate ( 56 ), represents the first preparation of this new heterocyclic ring. These compounds were examined for antiparasitic activity, however, no significant activity was detected.