Azinotriazines. I. Synthesis and spectral data of pyrido[3,2-e] -as-triazines

A series of pyrido[3,2-e]-as-triazines (VI) was prepared via acid-catalyzed cyclization of suitable 2-substituted 3-aminopyridines obtained by reduction of the corresponding 3-nitro-pyridines. Cyclization of 3-amino-2-hydrazinopyridines (III) with triethyl orthoformate and hydrochloric acid, or cyclodehydration of 2-(2-acetylhydrazino)-3-aminopyridines (IV) with alcoholic hydrogen chloride gave 1,2-dihydropyrido[3,2-e]-as-triazine hydrochloride (V). Mild dehydrogenation with alkaline potassium ferricyanide yielded heteroaromatic pyrido[3,2-e]-as-triazines (VI), for which ultraviolet and nmr spectral data are reported.     

Reactions with 5-aminopyrazoles. I. Synthesis of halogen-containing fused pyrazoles

5-Amino-3-phenylpyrazole (I) and 5-amino-4-bromo-3-phenylpyrazole (II) reacted with ethyl acetoacetate and acetylacetone to give various pyrazolo[1,5-a]pyrimidines IV-VI and with benzoins to give different fused pyrazoles, namely, imidazo[1,2-b]pyrazoles IX, pyrrolo[2,3-c]pyrazoles X and pyrazolo[4,3-b][1,4]oxazines XII. Diazotized II was coupled with active methylene-containing nitriles to afford pyrazolo[5,1-c]-as-triazines XIV.     

Ethylenimine derivatives of some 1,2,4-triazines

The first 3-ethylenimino-1,2,4-triazines ( 9 ) have been synthesized from the corresponding 3-(β-chloroethyl)amino-1,2,4-triazines ( 8 ). In addition some 2,3-dihydroimidazo[1,2-b]-1,2,4-triazines and imidazo[1,2-b]-1,2,4-triazines were obtained. The stability, properties and potential therapeutic value of these compounds are discussed.     

The synthesis of 7,8-dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]triazines

Cyclic hydrazino amidines were converted to the corresponding aminopyrazolyl derivatives. Ring closure between the amino groups of pyrazoline moieties and NH groups of cyclic amidines afforded the following ring systems: 7,8-Dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines.     

Diazo-, azo-, and azidoazoles. VII. Imidazo[1,2-b]- versus imidazo[2,1-c]benzo-as-triazines

Treatment of 3-aminobenzo-as-triazines with bromoacetaldehyde ethylene acetal give linear tricyclic imidazobenzo-as-triazines, where 3-amino-7-methylbenzo-as-triazine 1-oxide yields the angular isomer. The structures of these compounds have been established by comparing their nmr spectra to those of pyrazolo [5,1-c]- and s-triazolo[5,1-c]benzo-as-triazines obtained form the appropriate azo derivatives by intramolecular cyclization.     

Synthesis of 1H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazines, 8H-pyrazolo[3,4-e]tetrazolo[5,1-c]-as-triazine and 1,7-dihydro-8H-pyrazolo[3,4-e]-as-triazine derivatives

3-Hydrazino-7-methyl-5-phenyl-5H-pyrazolo[3,4-c]-as-triazine 1 underwent ring closure and/or condensation reaction with formic acid, acetic acid, acetic anhydride and benzoyl chloride to afford 1H-pyrazolo-[3,4-d]-s-triazolo[3,4-c]-as-triazines 2, 5 and 7a and/or N-acyl derivatives 3, 4 and 6 . N-Acyl derivatives 3 and 6 underwent cyclisation reaction on treatment with phosphoryl chloride to give 5 and 7a . 3-Methyl-1-phenyl-8-aryl-1H-pyrazolo[3,4-e]-s-triazolo[34,-c]-as-triazines 7 were also prepared by the reaction of the hydrazono derivatives 8 wit thionyl chloride. On treatment of 1 with nitrous acid gave the 8H-pyrazolo[3,4-e]tetrazolo-[5,1-c]-as-triazine 9 . Compound 1 underwent ring closure with carbon disulphide or ethyl chloroformate to 1,7-dihydro-8H-pyrazolo[3,4-e]-s-triazolo[3,4-c]-as-triazine derivatives 10 and 12 . Reaction of 1 with ethyl acetoacetate or acetylacetone gave 3-pyrazolo derivatives 13 and 14 .     

Condensed imidazo-1,24-azines. 28. Synthesis and transformations of 2-aroylmethyl-6,7.-diphenylimidazo-[1,2-b]-1,2,4-triazin-4H-3-ones

The reaction of 1,2-diamino-4,5-diphenylimidazole with 3-aroyl-2-propanonoic acid yields 2-aroylmethyl-6,7-diphenylimidazo[1,2-b]-1,2-4-triazin-4H-3-one. The cyclization pathways of these imidazoriazines leading to condensed furo[2,3-e]-, thieno[2,3-e]-, pyrrolo[2,3-e]-, and furo[3,2-e]limidazo[1,2,-b]-1,2,4-triazines were studied. A mass spectrometric study was carried out on the decomposition of these products upon electron impact. For Communication 27, see [1]. Kherson Industrial Institute, 325008 Kherson, Ukraine. A. N. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 117071 Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 258–262, February, 1998.     

Methyl imidazo[1,2-b]pyridazine-2-carbamates and related compounds as potential antifilarial agents

A series of imidazo[1,2-b]pyridazines have been synthesized for antifilarial evaluation. The compounds prepared include methyl 6-benzoylimidazo[1,2-b]pyridazine-2-carbamate ( 12 ), 6-benzoyl-2-t-butylimidazo[1,2-b]pyridazine ( 13 ), methyl 6-(4-fluorobenzoyl)imidazo[1,2-b]pyridazine-2-carbamate ( 14 ), and methyl 6-(2-thienylcarbonylcarbonyl)imidazo[1,2-b]pyridazine-2-carbamate ( 15 ) which are aza analogs of the anthelmintic agents mebendazole, flubendazole and nocadazole. In addition, the preparation of a series of 2-t-butylimidazo[1,2-b]-pyridazine-6-carboxylic acid derivatives is described. Electrophilic bromination and iodination substitutions of 2-t-butyl-6-methylimidazo[1,2-b]pyridazine afforded 3-halo derivatives. Methyl 6-(4-fluorobenzoyl)pyridazine-3-carbamate was also prepared for antifilarial evaluation. None of these compounds possessed significant antifilarial activity against Brugia pahangi or Acanthocheilonema viteae infections in jirds.     

Synthesis of 5-methylfuro[3,2-b]pyridine-2-carboxylic acid

Oxidation of 3-hydroxy-6-methyl-2-hydroxymethylpyridine with manganese dioxide yielded the corresponding aldehyde, the condensation of which with diethyl bromomalonate furnished hydroxydihydrofuro[3,2-b]pyridinediearboxylie acid ester. Saponification of the diester with concentrated hydrochloric acid afforded the hydrochloride of 5-methylfuro[3,2-b]pyrjdine car-boxylic acid.     

A facile synthesis of 1-alkylthio and acylthio-2,3-dihydro-1H-naphtho[2,1-b]thiopyrans and 4-alkylthio and acylthio-3,4-dihydro-2H-naphtho[1,2-b]thiopyrans

The reaction of 3-(2-naphthylthio)propionaldehyde ( 3 )and its (1-naphthylthio)isomer (7)with a variety of thiols and thio acids in the presence of sulfuric acid at room temperature afforded 1-alkylthio and acylthio-2,3-dihydro-1H-naphtho[2,1-b]thiopyrans 5 and 4-alkylthio and acylthio-3,4-dihydro-2H-naphtho[1,2-b]thiopyrans 9 in excellent yield.     

Ring transformation of 1,5-benzoxazepines into spirobenzoxazoles. Synthesis of pyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines and spiro[benzoxazole-2′(3′H),4(1H)-pyrazolo[5,1-c][1,2,4]triazines]

The reactions of the 3-substituted 4-amino-8-ethoxycarbonyl[5,1-c][1,2,4]triazines 1 and 2 with o-amino-phenol hydrochloride gave the pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzoxazepines 5 and 8 . The alkylation of 5 with methyl iodide and isopropyl iodide afforded the 6-alkoxylpyrazolo[1′,5′:3,4][1,2,4]triazino-[5,6-b][1,5]benzoxazepines 6a and 6b , respectively. Refluxing of 5, 6a, 6b and 8 in hydrochloric acid/acetic acid resulted in ring transformation to produce the spiro[benzoxazole-2′(3′H),4(1H)pyrazolo[5,1-c][1,2,4]-triazines] 7a, 7b and 9 . The screening data of the above compounds was described.     

Etude de la réaction de l'acé'tylacé'tate d'éthyle avec les diamino-1,5 imidazoles

The condensation of 1,5-diaminoimidazoles with ethyl aceto-acetate gives two types of compounds: imidazo[1,5-b]-1,2,4-triazepinones and imidazo[4,5-b]pyridinones. The structure of these compounds is demonstrated by rmn and mass spectroscopy. The formation of imidazo[4,5-b]pyridinones from imidazo[1,5-b]-triazepinones through a new transposition is also shown.     

The synthesis and properties of pyridazino[4,3-e] -as-triazines and pyridazino[4,5-e] -as-triazines,two novel condensed pyridazine ring systems

The compounds prepared in the novel pyridazino[4,3-e]-as-triazine ring system are: 8-chloro-4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 21 ), 8-chloro-2,4-dimethyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 23 ), 8-chloro-2-ethyl-4-methyl-3,4-dihydropyridazino[4,3-e]-as- triazine ( 24 ), 4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine-8-thione ( 25 ), 4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 26 ), 2,4-dimethyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 27 ), and 2-ethyl-4-methyl-3,4-dihydropyridazino[4,3-e]-as-triazine ( 28 ). In the novel pyridazino[4,5-e]-as-triazine ring system the following compounds were prepared: 1,2-dihydropyridazino[4,5-e]-as-triazine ( 31 ), 3-methyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 32 ), 3-ethyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 33 ), and 1-methyl-1,2-dihydropyridazino[4,5-e]-as-triazine ( 35 ). The preparation of a number of previously unreported intermediates and compounds for structure proof are also described.     

Acetylenchemie. 9. Mitt. Anellierte imidazole aus N-propinylamid-vorstufen

The Compound 2-(N-Formyl-N-prop-2′-inyl)aminopyridine was cyclised in boiling formic acid to 3-methylimidazo[1,2-a]pyridine, with 3-methylene-2H-imidazo[1,2-a]pyridine as the intermediate. Under similar conditions the 1,3-diprop-2-inylpyrimido[4,5-b]quinoline-2,4-dione resulted from 1-methylimidazo[1,2-a]quinoline-4-carbonic acid-N-2-prop-2′-inylamide and from the 1-prop-2′-inylbenzo[b][1,8]naphthyridin-2-one the 1-methylbenzo[b]imidazo[1,2,3-ij]naphthyridine-4,7-dione as a new ring system, was obtained.     

Photocyclization of 2-(naphth-1-yl)-3-(thien-2-yl)propenoic acid and the total assignment of the 1H- and 13C-NMR spectra of the product

Photocyclization of the substituted 2-(naphth-1-yl)-3-(thien-2-yl)propenoic acid ( 3 ) in the presence of iodine and air in a benzene-cyclohexane mixture afforded a separable mixture of three compounds, phenanthro[2,1-b]thiophene-10-carboxylic acid ( 4 ), phenanthro[2,1-b]thiothene ( 5 ), and naphtho[1,8-cde]-thieno[3,2-g][2]benzopyran ( 6 )     

Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.     

Furopyridines. III. A new synthesis of furo[3,2-b]pyridine

A convenient synthesis of furo[3,2-b]pyridine and its 2- and 3-methyl derivatives from ethyl 3-hydroxypiconate ( 1 ) is described. The hydroxy ester 1 was O-alkylated with ethyl bromoacetate or ethyl 2-bromopropionate to give the diester 2a or 2b . Cyclization of compound 2a afforded ethyl 3-hydroxyfuro[3,2-b]pyridine-2-carboxylate ( 3 ) which in turn was hydrolyzed and decarboxylated to give furo[3,2-b]pyridin-3-(2H)-one ( 4a ). Cyclization of 2b gave the 2-methyl derivative 4b . Reduction of 4a and 4b with sodium borohydride yielded the corresponding hydroxy derivative 5a and 5b respectively, which were dehydrated with phosphoric acid to give furo[3,2-b]pyridine ( 6a ) and its 2-methyl derivative ( 6b ). 2-Acetylpyridin-3-ol ( 8 ) was converted to the ethoxycarbonylmethyl ether ( 9 ) by O-alkylation with ethyl bromoacetate, which was cyclized to give 3-methylfuro[3,2-b]pyridine-2-carboxylic acid ( 10 ). Decarboxylation of 10 afforded 3-methylfuro[3,2-b]pyridine ( 11 ).     

Studies on heterocyclic compounds. VII. Syntheses of novel furo[2, 3-b]chromones

Furo[2, 3-b]chromone ( 1a ) was conveniently prepared by the PPE-promoted cyclization of 5-(2′-carboxy-phenoxy)furan-2-carboxylic acid ( 8 ) which was made from methyl salicylate and ethyl 5-nitrofuran-2-carboxyl-ate. Furo[2, 3-b]chromon-2-acrylic acid ( 13 ) was obtained by a similar cyclization. Direct acylation of 1a afforded 2-acetylfuro[2, 3-b]chromone ( 10 ). Several derivatives of furo[2, 3-b]chromone were found to display activity in the rat passive cutaneous anaphylaxis (PGA) test for antiallergic activity.     

Methyl 2-benzoylamino-3-dimethylaminopropenoate in the synthesis of heterocyclic systems. An attempt to prepare benzoylamino substituted azolo- and azinopyrimidines with a bridgehead nitrogen atom

Methyl 2-benzoylamino-3-dimethylaminopropenoate ( 2 ) was introduced as a new reagent for the preparation of fused pyrimidinones 4 from heterocyclic α-amino compounds in acetic acid. In this manner, derivatives of pyrido[1,2-a]pyrimidine 4a,b,f , pyrimido[1,2-b]pyridazine 4g , pyrimido[1,2-c]pyrimidine 4j , pyrazino[1,2-a]pyrimidine 4k , thiazolo[2,3-b]pyrimidine 41 , pyrazolo[1,5-a]pyrimidine 4m , and 1,2,4-triazolo-[1,5-a]pyrimidine 4n were prepared.     

Transformations of isomeric naphthopyranones. The synthesis of substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives

The opening of the pyranone ring in 2H-naphtho[1,2-b]pyran-2-one derivative (1) and 3H-naphtho[2,1-b]-pyran-3-one derivatives 8 and 20 with nucleophiles afforded 3-(naphthyl-1)- and 3-(naphthyl-2)propenoates (substituted β-naphthyl-α,β-dehydro-α-amino acid derivatives) 7, 13, 14, 15, 24 , and 35 .