Heterocyclic derivatives of purines. 3. Synthesis and mass spectrometric study of imidazo[1,2-]purine

A mixture containing 65% 1-methyl-2-phenyl-5,7-dichloro- and 35% 1-methyl-2-phenyl-3,5,7-trichloroimidazo [1,2-f] purine (the percentages of the components were established by means of Chromatographic mass-spectrometric analysis) was obtained by refluxing 1,8-dimethyl-2-phenylimidazo [1,2-f]xanthine in POCl₃ in the presence of excess PCl₅. Reduction of this mixture with concentrated HCl in the presence of red phosphorus leads to 1-methyl-2-phenylimidazo[1,2-f] purine, while heating with piperidine gives a mixture consisting of 55% 1-methyl-2-phenyl-6-piperidino-8-chloroimidazo [1,2-f] purine and 45% 1-methyl-2-phenyl-3, 8-dichloro-6-piperidino-imidazo [1,2-f] purine. The IR, PMR, and mass spectra of the compounds obtained are discussed.See [1] for communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125–1129, August, 1980.     

Diethyl ethoxymethylenemalonate in triheterocycles: A new synthesis of pyrido[3,2-e]pyrimido[1,2-c]pyrimidines

Diethyl ethoxymethylenemalonate was used for the novel synthesis of the triheterocyclic 3-carbethoxy-9,ll-disubstituted-4-oxo-4H-pyrido[3,2-e]pyrimido[1,2-c]pyrimidines from 4-aminopyrido[2,3-d]pyrim-idines via thermal cyclization of the intermediate ethyl 2-carbethoxy-3-[5,7-disubstituted-4-amino-pyrido[2,3-d]pyrimidin-4-yl]acrylates. The alkaline hydrolysis of 3-carbethoxy-4-oxo-4H-pyrido[3,2-e]-pyrimido[1,2-c]pyrimidines was performed to give corresponding acid derivatives.     

Synthesis and properties of 1-aryl-1,4-dihydro-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidine-6-carboxylic acids and their derivatives

Acetylation of 2-arylamino-5-carbethoxy-6-methylnicotinonitriles gave N-acetyl-2-arylamino-5-carbethoxy-6-methylnicotinonitriles, which, under the influence of hydrogen chloride, are cyclized to 1-aryl-1,4-dihydro-6-carbethoxy-2,7-dimethyl-4-oxopyrido[2,3-d]pyrimidines. The latter can be converted to the corresponding carboxylic and hydroxamic acids, as well as to acetylation products 1-aryl-2-acetonyl-1,4-dihydro-6-carbethoxy-7-methyl-4-oxopyrido [2,3-d]pyrimidines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 535–539, April, 1992.     

Synthesis of 3-amino derivatives of benzo[b]furo[2,3-c]pyridines

The reaction of 1,7-dimethyl-3(2H)-benzo[b]furo[2,3-c]pyridone with phosphoric acid amides gave 1,7-dimethyl-3-dimethylamino (morpholino)benzo[b]furo[2,3-c]pyridines. A method for the synthesis of 3-amino derivatives of 4-nitrobenzo[b]furo[2,3-c]pyridines, which consists in heating 1,7-dimethyl-4-nitro-3(2H)-benzo[b]furo[2,3-c]pyridone with hexamethyldisilazane and secondary or primary amines in pyridine, was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1555, November, 1991.     

Facile assembly of fused benzo[4,5]furo heterocycles

A concise synthesis of fused benzo[4,5]furo heterocycles 18 has been developed. Chemo/regioselective Suzuki coupling between 1,2-dihaloarene 17 and alpha-hydroxyphenylboronic acid or ester 20 gives biaryl phenol 19, which then undergoes copper(I) thiophene-2-carboxylate (CuTC)-mediated intramolecular cyclization to afford 18 in good overall yield. This method has broad substrate scope and allows facile assembly of a wide variety of benzo[4,5]furo heterocycles.     

Synthesis and reactions of benzo[b]furo[2,3-c]pyrylium salts

A method has been developed for the synthesis of 3-acetonyl- and 3-phenacylben-zo[b]furans by cyclization of 1-arloxy-2,4-pentanediones and 1-phenyl-4-aryloxy-1,3-butanediones in polyphosphoric acid. Acylation of 3-acetonyl(phenyl-benzo-[b]furans with aliphatic acid anhydrides in the presence of perchloric acid gives the benzo[b]furo[2,3-c]pyrylium perchlorates. The recyclization of the pyrylium salts with ammonia, aqueous alkali, and morpholine has been examined.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 889–893, July, 1987.     

Condensed pyridine bases. A new approach to the synthesis of 3-phenacylbenzo[b]thiophenes and 3-phenacyl-5-ethylthieno[2,3-b]thiophene. Synthesis of new derivatives of benzothieno[2,3-c]pyrylium and thieno[2′,3′:5,4]thieno-[2,3-c]pyrylium and pyridine bases

A new method is proposed for the production of substituted 3-phenacylbenzo[b]thiophenes by the intramolecular cyclization of 1-phenyl-4-phenylthio-1,3-butanediones in polyphosphoric acid. The analogous cyclization of 1-phenyl-4-(5-ethyl-2-thienylthio)-1,3-butanedione leads to 3-phenacyl-5-ethylthieno[2,3-b]thiophene. The acylation of substituted 3-phenacylbenzo[b]thiophenes and 3-phenacyl-5-ethylthieno[2,3-b]thiophene by the anhydrides of aliphatic acids in the presence of perchloric acid leads to 1-alkyl-3-phenylbenzothieno[2,3-c]pyrylium perchlorates and 2-ethyl-5-phenyl-7-methylthieno[2′,3′:5,4]thieno[2,3-c]pyrylium perchlorate. The action of ammonium acetate on the obtained salts gives the corresponding pyridine bases. L. M. Litvinenko Institute of Physical Organic Chemistry and Coal Chemistry, National Academy of Sciences of Ukraine, Donetsk 340114. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1335–1339, October, 1998.     

Synthesis of condensed structures from 3-cyano-2-pyridylacrylic acids

Ammonolysis of the methyl esters of trans--(3-cyano-2-pyridyl)acrylic (I) and trans--(6-methyl-3-cyano-2-pyridyl)acrylic (II) acids gave the amides of these acids. The addition of bromine, diazomethane, and hydrogen to the double bond of cis- and trans-acids I and II is described. Hydrogenation of the methyl esters of trans-acids I and II over Raneynickel at room temperature and atmospheric pressure occurs with intramolecular cyclization to two-ring lactams — 7-oxo-5, 6,8,9-tetrahydropyrid[3,2-c]azepine and 2-methyl-7-oxo-5,6,8,9-tetrahydropyrid[3,2-c]azepine. Under the conditons of acid hydrolysis of acids I and II the elements of water add to the nitrile group with intramolecular cyclization to give, respectively, 3-carboxymethyl-1-oxo-2,3-dihydrofuro [4,3-b]pyridine and 5-methyl-3-carboxymethyl-1-oxo-2,3-dihydrofuro[4,3-b]pyridine, whereas refluxing these acids with aqueous sodium hydroxide gives two-ring lactams — 3-carboxymethyl-1-oxo-2, 3-dihydropyrrolo[4,3-b]pyridine and its 5-methyl homolog. The structures of the compounds were confirmed by the UV, IR, PMR, and mass spectra.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 63–69, January, 1978.     

Synthesis of 2-selenothieno[2,3-d]pyrimidine derivatives

Intramolecular cyclization of 2-(N-acylselenoureido)-3-carbethoxy-4,5,6,7-tetrahydrobenzo[b]thiophenes in alkaline media leads to the formation of the potassium salt (I) of 2-seleno-4-oxo-3,4,5,6,7,8-hexahydrobenzo[b]thieno[2,3-d]pyrimidine, acidification of which yielded the corresponding base in free form. Some pyrimidine compounds containing a selenium atom in the side chain were obtained by reaction of potassium salt I with halo derivatives (ClCH₂CH₂COOCH₃ and ClCH₂CH₂OH).Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–754, June, 1977.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

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.     

Polycyclic N-heterocyclic compounds. 48. syntheses of furo[2,3-h]-[1,6]naphthyridine and imidazo(or pyrimido)[2,1-f]-[1,6]naphthyridines with rearrangement

The formation of a novel ring system, furo[2,3-h][1,6]naphthyridine via the Smiles rearrangement and intramolecular cyclization is described. Cyclization of 5-(ω-hydroxyalkylamino)-8-methyl-1,2-dihydrofuro[2,3-h][1,6]naphthyridines provided novel spiro compound with rearrangement.     

2,5-Dimethyl-4-(p-aminobenzyl)pyridine in the synthesis of substituted quinolines,pyridoindazoles, and isoquinolinoquinolines

2,5-Dimethyl-4-pyridyl(6-quinolyl)methane was obtained from 2,5-dimethyl-4-(p-aminobenzyl)pyridine via the Skraup reaction. The product was nitrated to 2,5-dimethyl-4-pyridyl (5-nitro-6-quinolyl)methane, which was reduced to 2,5-dimethyl-4-pyridyl (5-amino-6-quinolyl)methane. It was established that the diazo compound formed from this amino derivative is converted to 1H,3-(2,5-dimethyl-4-pyridyl)-pyrido [2,3-g]indazole as a result of intramolecular cyclization. 9-Methyliso-quinolino [7,6-f]quinoline was obtained by catalytic dehydrocyclization of 2,5-dimethyl-4-pyridyl (6-quinolyl)methane. 2,5-Dimethyl-4-pyridyl(5-nitro-6-quinolyl)methane has chemochromic properties.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 677–680, May, 1980.     

Synthesis of furo[2,3-d]pyrimidines condensed with a tetrahydrothiopyran

Using o-iodobenzoic acid we synthesized 5-hydroxy-2,2-dimethyltetrahydrothiopyran-4-one. From the latter we synthesized 2-amino-5,5-dimethyl-3-cyano-4,5-dihydro-7H-furo[2,3-c]thiopyran; this is a starting material for the preparation of furo[2,3-d]pyrimidine condensed with tetrahydrothiopyran and triazole rings.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1403–1405, October, 1990.     

Polymethine dyes — Furo[3,2-f]quinol-7-yl and furo[3,2-f]quinol-9-yl derivatives

New heterocyclic bases — 7- and 9-methylfuro[3,2-f]quinolines — were synthesized by condensation of 5-aminobenzofuran double tin hydrochloride salt with paraldehyde in dilute hydrochloric acid and with methyl vinyl ketone in ethanol in the presence of ferric chloride and zinc chloride. Polymethine dyes of various types were obtained from the quaternary salts of the synthesized bases. The introduction of a furan ring in the 5,6 position of quino-2- and quino-4-carbocyanines gives rise to a smaller bathochromic effect than the analogous introduction of a thieno and, particularly, a benzo group.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 391–394, March, 1977.     

Investigation of nitrogen- and sulfur-containing heterocycles. 44. New heterocyclic systems. Derivatives of imidazolidino-[3,2-f]pyrido[2,3-b]-and imidazolidino[3,2-f]pyrimido[4,5-b]-1,4-thiazines. Synthesis and structure

New representatives of heterocyclic systems, imidazolidino[3,2-f]-pyrido-[2,3-b]- and imidazolidino[3,2-f]pyrimido[4,5-b]-1,4-thiazines, have been obtained. Intermediate compounds of 5N-oxalamides-6-hydroxy-7H-pyrido[2,3-b]-1,4-thiazine have been isolated and characterized. Amides of N-(pyridyl-3)- and N-(pyrimidyl-5)-oxaminic acids have been obtained.For communication 43, see [1].Translated from Khimiya Geterotsiklicheskikh Soedininii, No. 7, pp. 992–997, July, 1986.     

The transformation of saccharin into derivatives of lmidazo[1,2-b] [1,2]-benzisothiazole and benzo[g] [1,2,5]thiadiazocine

Reaction of 3-(2-hydroxyethylamino) benzo[d]isothiazole 1,1-dioxide ( 5a ) with thionyl chloride gives a mixture of the expected chloroethyl derivative ( 5h ) and the rearranged saccharin 2-(2-aminoethyl)-3-oxo-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide hydrochloride ( 6a ). Separate treatment of the chloroethyl compound ( 5h ) with dilute alkali gives the expected cyclization product 2,3-dihydroimidazo[1,2-b] [1,2] benzisothiazole 5, 5-dioxide ( 7a ). Acidification of the liquors of the above reaction yields the ring expanded derivative 6-oxo-3,4,5,6-tetrahydro-[2H]benzo[g][1,2,5]thiadiazocine 1,1-dioxide ( 12f ), a representative of a new ring-system. Treatment of the imidazo derivative ( 7a ) with concentrated hydrochloric acid again yields the N-substituted saccharin ( 6a ) which upon treatment with alkali also produces the thiadiazocine ( 12f ). In contrast, treatment of the imidazo compound ( 7a ) with alkali leads to attack on the sulphonamide function to give 2-(2-imidazolin-2-yl)benzenesulphonic acid ( 8 ). It is suggested that the multitude of chemical interconversions which can be induced within this series of compounds (Scheme II) can only be accounted for if two separate cyclol intermediates are invoked. Related reactions observed with variously substituted derivatives of the starting saccharin derivative ( 5a ) are discussed as are the spectral properties and chemical reactivity of the new compounds prepared.     

A novel tandem cyclization of condensed 2,3-dialkynylpyrazines into [1,2,3]triazolo[1′,5′;1,2]pyrido[3,4-b]pyrazines promoted by sodium azide

6,7-Dialkynyl-1,3-dimethylpteridine-2,4(1H,3H)-diones and 2,3-dialkynylquinoxalines have been shown to react with sodium azide in DMF at room temperature giving rise 9,11-dimethyl-[1,2,3]triazolo[1′,5′;1,2]pyrido[4,3-g]pteridine-8,10(9H,11H)-diones and [1,2,3]triazolo[1′,5′;1,2]pyrido[3,4-b]quinoxalines. A novel tandem cyclization involves 1,3-dipolar cycloaddition of an azide ion to the carbon-carbon triple bond followed by intramolecular nucleophilic addition of the intermediate 1,2,3-triazole N-anion to another CC bond.     

Synthesis of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones

1-R-9,9,9a-Trimethyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones and the corresponding 2-methylene-2,3-dihydroindoles were obtained by the reaction of 2,3,3-trimethyl-3H-indole with a number of N-substituted chloroacetic acid amides and subsequent reaction of the resulting quaternary salts with bases. The kinetics of intramolecular cyclization of 1-(N-alkylcarbamoylethyl)-2-methylene-2,3-dihydroindoles under the influence of acetic acid were studied. Under the influence of strong protic acids 1-R-imidazo[1,2-a]indol-2-ones undergo decyclization and are converted to 3H-indolium salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1485–1489, November, 1986.     

Pyrroloindoles. 6. New synthesis of 1H, 5H-pyrrolo[2,3-f]indole and 3H,6H-pyrrolo[3,2-e]indole

Ethyl pyruvate 1-acetyl-5-indolinylhydrazone was obtained by diazotization of 1-acetyl-5-aminoindoline with subsequent reduction of the diazonium salt and condensation of the hydrazine with ethyl pyruvate. A mixture of hydrogenated derivatives of linear and angular pyrroloindoles is formed as a result of cyclization of the hydrazone in polyphosphoric acid esters. Subsequent hydrolysis, decarboxylation, and dehydrogenation lead to 1H,5H-pyrrolo[2,3-f]indole and 3H,6H-pyrrolo-[3,2-e]indole.See [1] for Communication 5.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 504–507, April, 1982.