Synthesis of 8-methyl-2-azainosine and related nucleosides

The synthesis of 6-methyl-7-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azainosine ( 2) ) and 6-methyl-7-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 5 ) by diazotization of 5-amino-1-(β-D-ribofuranosyl)-2-methylimidazole-4-carboxamide ( 1 ) and diazotization of 5-amino-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2-methylimidazole-4-carboxamide ( 3 ), followed by deacetylation of the resulting compound 4 , is described. The preparation of 6-methyl-5-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one ( 10 ) and 6-methyl-5-(β-D-glucopyranosyl)imidazo[4,5-d]-v-triazin-4-one ( 11 ) by glycosylation of 6-methylimidazo[4,5-d]-v-triazin-4-one (8-methyl-2-azahypoxanthine, ( 7) ) is also described. Structural assignments were made on basis of analytical and ¹H-nmr and uv spectral data.     

Synthesis and antiviral evaluation of some novel [1,2,4]triazolo[4,3-β][1,2,4]triazole nucleoside analogs

Ribosylation of 3-amino-5H-[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 1 ) with l-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose and stannic chloride resulted in the following protected nucleoside analogs: 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 4 ), 3-amino-1-(2,3,5-tri-O-benzoyl-α-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), 3-amino-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)[1,2,4]triazolo[4,3-β][1,2,4]triazole ( 5 ), and 3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl) amino-5H-[1,2,4]triazolo[4,3-b]-[1,2,4]triazole ( 7 ). Compounds 4–6 were deprotected to 3-amino-1-β-D-ribofuranosyl[1,2,4]triazolo[4,3-b][1,2,4]-triazole ( 3 ), 3-amino-1-α-D-ribofuranosyl[1,2,4]triazolo[4,5-b][1,2,4]triazole ( 8 ), and 3-imino-2H-2-β-D-ribo-furanosyl[1,2,4]triazolo[4,3-b][1,2,4]triazole ( 9 ), while 7 could not be deprotected without decomposition. Compounds 1, 4, 6, 7 , and 9 were screened and found to have no antiviral activity.     

Synthesis of imidazo[4,5-d]pyridazine nucleosides related to inosine

Several imidazo[4,5-d]pyridazine nucleosides which are structurally similar to inosine were synthesized. Anhydrous stannic chloride-catalyzed condensation of persilylated imidazo[4,5-d]-pyridazin-4(5H)one (1) and imidazo[4,5-d]pyridazine-4,7(5H,6H)dione ( 16 ) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose ( 3 ) provided (after sodium methoxide deblocking) 6-β-D-ribo furanosylimidazo[4,5-d]pyridazin-4(5H)one (5) and 3,6-di-(β-D-ribofuranosyI)imidazo[4,5-d]pyridazin-4-one ( 7 ); and 1-(β-D-ribofuranosyl)imidazo[4,5-d]pyridazine-4,7(5H,6H)dione ( 19 ) and 1,5 or 6-di-(β-D-ribofuranosyl)imidazo[4,5-d ]pyridazine-4,7(5H or 6H)dione ( 21 ), respeeitvely. 4,7-Diehloro-1-β-D-ribofuranosylimidazo[4,5-d]pyridazine ( 12 ) and dimethyl 1-β-D-ribofuranosylimidazole-4,5-dicarboxylate ( 26 ), both prepared from stannic chloride-catalyzed ribosylations of the corresponding heterocycles, were converted in several steps to 3-β-D-ribo-furanosy limidazo[4,5-d]pyridazin-4(5H)one ( 14 ) and nucleosidc 19 , respectively. Acid-catalyzed isopropylidenation of mesomeric betaine 7 or nuclcoside 14 provided 3-(2,3-isopropylidene-β-D-ribofuranosyl)imidazo[4,5-d]pyrizin-4(5H)one ( 31 ). 1-β-D-Ribofuranosylimidazo[4,5-d]-pyridazine ( 29 ) was obtained in several steps from nueleoside 12 . The structure of the nucleosides was established by the use of carbon-13 and proton nmr.     

Synthesis and biodistribution of p-iodophenyl analogues of a naturally occurring imidazole ribonucleoside

A model iodophenyl imidazole ribonucleoside has been synthesized to study biodistribution properties in laboratory animals. The key intermediate 5-amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-[N-(p-iodophenyl)carboxamide] ( 5 ) was synthesized by coupling N-succinimidyl-5-amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxylate ( 4 ) and p-iodoaniline. Deacetylation of the intermediate compound gave 5-amino-1-β-D-ribofuranosylimidazole-4-[N-(p-iodophenyl)]carboxamide ( 6 ). Ring annulation via diazotization of 5 gave 7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-[3-N-(p-iodophenyl)]-4-one ( 7 ). Subsequent deacetylation of 7 afforded 7-β-D-ribofuranosylimidazo[4,5-d]-v-triazin-[3-N-(p-iodophenyl)]-4-one ( 8 ). The radiolabeled compounds, [¹²⁵I] 5 and [¹²⁵I] 6 were prepared in a manner similar to the corresponding unlabeled compounds except that p-[¹²⁵I]iodoaniline was used for coupling with 4 . Biodistribution studies of iodine-125-labeled 5 and 6 were performed in female Fischer rats and tumor bearing nude mice. Compound 6 showed uptake in the brain and proliferating tissues such as tumor and bone-marrow.     

Synthesis of 6-amino-1,2,3-triazolo[4,5-c] pyridin-4(5H)one (8-aza-3-deazaguanine) and 6-amino-1-(β-D-ribofuranosyl)-1,2,3-triazolo[4,5-c] pyridin-4(5H)one (8-Aza-3-deazaguanosine) via novel ring closure procedures

The total synthesis of 6-amino-1,2,3-triazolo[4,5-c]pyridin-4(5H)one (8-aza-3-deazaguanine, 3 ) and 6-amino-1-(β-D-ribofuranosyl)-1,2,3-triazolo[4,5-c]pyridin-4(5H)one (8-aza-3-deazaguano-sine, 22 ) has been described for the first time by a novel base-catalyzed ring closure of 4(5)-cyanomethyl-1,2,3-triazole-5(4)carboxamide (14) and methyl 5-cyanomethyl-1-(2,3,5-tri-O-ben-zoyl-β-D-ribofuranosyl)-1,2,3-triazole-4-carboxylate (17) , respectively. Under the catalysis of DBU, 2,4-dinitrophenylhydrazone of dimethyl 1,3-acetonedicarboxylate (7) was converted to methyl 5-methoxycarbonylmethyl-1-(2,4-dinitroanilino)-1,2,3-triazole-4-carboxylate (12) via dimethyl 2-diazo-3-iminoglutarate (8) . Catalytic reduction of 12 gave methyl 4(5)methoxycar-bonylmethyl-1,2,3-triazole-5(4)carboxylate (11) from which methyl 4(5)carbamoylmethyl-1,2,3-triazole-5(4)carboxylate (10) was obtained by ammonolysis. Dehydration of 10 provided methyl 4(5)cyanomethyl-1,2,3-triazole-5(4)carboxylate (13) which on amination gave 14 . The 1,2,3-triazole nucleosides 17, 18 and 19 were obtained from the stannic chloride-catalyzed condensation of the trimethylsilyl 13 and a fully acylated β-D-ribofuranose. The yield and ratio of the ribofuranosyl derivatives of 13 markedly depends on the ratio of stannic chloride used. The structures of the nucleosides 22 and 23 were established by a combination of NOE, ¹H-nmr and ¹³C-nmr spectroscopy.     

The synthesis of 2-azainosine and related derivatives by ring annulation of imidazole nucleosides

The synthesis of 7-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one ( 6b , 2-azainosine) and 5-(β-D-ribofuranosyl)imidazo[4,5-d]-v-triazin-4-one ( 4b ) have been achieved for the first time by direct diazotization of AICA riboside ( 5b ) and iso-AICA riboside ( 3b ), respectively. The conditions required for cyclization of the model methyl bases, 3a and 5a , as well as the nucleosides 3b , 5b , and 7 are described.     

Pyrrolopyrimidine nucleosides. IV. The synthesis of certain 4,5-disubstituted-7-(β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidines related to the pyrrolo[2,3-d]pyrimidine nucleoside antibiotics

The treatment of 4-chloro-7-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 4 ) with N-bromoacetamide in methylene chloride has furnished the 5-bromo derivative of 4 which on subsequent deacetylation provided a good yield of 5-bromo-4-chloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d] pyrimidine ( 6 ). Assignment of the halogen substituent to position 5 was made on the basis of pmr studies. Treatment of 6 with methanolic ammonia afforded 4-amino-5-bromo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d ]pyrimidine ( 8 , 5-bromotubercidin) and a subsequent study has revealed that the 4-chloro group of 6 was replaced preferentially in a series of nucleophilic displacement reactions. The analogous synthesis of 4,5-dichloro-7-(β-D-ribo-furanosyl)pyrrolo[2,3-d]pyrimidine ( 13b ) and 4-chloro-5-iodo-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine ( 13a ) from 4 furnished 5-chlorotubercidin ( 15 ) and 5-iodotubercidin ( 14 ), respectively, on treatment of 13b and 13a with methanolic ammonia. The possible biochemical significance of these tubercidin derivatives is discussed.     

The synthesis of 3-(β-D-ribofuranosyl)imidazo[4,5-c] pyridazines

7-Chloro-3-(β- D -2,3,5-tri-O-benzoylribofuranosyl)imidazo[4,5-c] pyridazine ( 3 ), obtained from the condensation of 7-chloro-3-trimethylsilylimidazo[4,5-c] pyridazine ( 1 ) with 2,3,5-tri-O-benzoyl- D -ribofuranosyl bromide ( 2 ), served as the percursor of 7-chloro- ( 4 ), 7-amino- ( 8 ), and 7-mercapto-3-(β- D -ribofuranosyl)imidazo[4,5-c] pyridazine ( 9 ). 3-(β- D -ribofuranosyl)imidazo[4,5-c] pyridazine ( 7 ) was obtained from 3-(β- D -2,3,5-tri-O-benzoylribofuranosyl)imidazo-[4,5-c]pyridazine ( 6 ). The site of ribosidation is based upon uv spectral comparisons with model methyl compounds. The assignment of the anomeric configuration is derived from pmr spectral data.     

Synthetic studies of potential antimetabolites. XIII. Synthesis of 7-amino-3-β-d-ribofuranosyl-3H-imidazo[4,5-b] pyridine (1-deazaadenosine) and related nucleosides

7-Amino-3-β-D-ribofuranosyl-3H-imidazo[4,5-b]pyridine (III, 1-deazaadenosine) was synthesized in 32% yield from the diacetyl derivative prepared from 7-aminoimidazo[4,5-b ]pyridine (1-deazaadenine) and 1,2,3,5-tetra-O-acetyl-β-D-ribose by the fusion method. A synthesis of 7-amino-4-b?-D-ribofuranosyl-4H-imidazo[4,5-b]pyridine (IV) was also achieved.     

Synthesis of 1-and 3-substituted imidazo[4,5-b]pyridin-2-ones

1-and 3-Substituted imidazo[4,5-b]pyridin-2-ones were synthesized by heating equimolar amounts of 3-amino-2-chloropyridine or 2-chloro-3-methylaminopyridine, urea, and the corresponding arylamine at 150–210°C. The reaction of 3-amino-2-chloropyridine with urea and p-phenylenediamine or p,p′-diaminobiphenyl at a ratio of 2:2:1 under analogous conditions gave 1,4-bis-(2-oxoimidazo[4,5-b]pyridin-3-yl)benzene or 1,4-bis(2-oxoimidazo[4,5-b]pyridin-3-yl)biphenyl, respectively.     

4-(3-Cyanopyridin-2-ylthio)acetoacetates in synthesis of heterocycles

Substituted 2-amino-4-aryl-3-cyano-5-oxo-5,6-dihydro-4H-pyrano[2,3-d]pyrido[3",2":4,5]thieno[3,2-b]pyridines were synthesized by the reactions of 4-hydroxy-1H-thieno[2,3-b;4,5-b]dipyridin-2-ones with arylidenemalononitriles or by the three-component reactions of hydroxythienodipyridinones with aldehydes and malononitrile in DMF in the presence of triethylamine. Methods for syntheses of substituted 3-alkoxycarbonyl-6-amino-4-aryl-2-(3-cyanopyridin-2-ylthiomethyl)-4H-pyrans were developed on the basis of the reactions of 4-(3-cyanopyridin-2-ylthio)acetoacetates and arylidenemalononitriles or aldehydes and malononitrile. Ethyl 4-(3-cyanopyridin-2-ylthio)acetoacetate and 4-methoxybenzylidenecyanothioacetamide were used for the synthesis of 6-(pyridin-2-ylthiomethyl)-3-cyanopyridine-2(1H)-thione.     

New process for the synthesis of imidazo[4,5-b]pyridine derivatives as potent orally active thromboxane a2 receptor antagonists

A new synthetic route to prepare the 4-[3-(4-chlorophenyl)methyl-6-chloroimidazo[4,5-b]pyridin-2-yl]-3,3-dimethylbutanoic acid (UP 116-77) is described. UP 116-77 is a potent orally active TXA₂/PGH₂ receptor antagonist currently under pharmacological investigation. Its development needed a suitable synthesis for industrial processing. The cyclization of 3-amino-5-chloro-2-(4-chlorophenyl)methylaminopyridine 4 with 3,3-dimethylglutaric anhydride in refluxing acetic acid affords a new efficient and simple way to UP 116-77 and subsequently to various 2-substituted imidazo[4,5-b]pyridine derivatives.     

Synthesis of 8-amino-4-methylthio-6-methyl-2-(β-D-ribofuranosyl)-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene and an unusual reductive ring-opening of the 1,2,3,5,6,7-hexaazaacenaphthylene ring system

The tricyclic nucleoside 8-amino-4-methylthio-6-methyl-2-(β-D-ribofuranosyl)-1,2,3,5,6,7-hexaazaacenaphthylene ( 3 ) was synthesized from 3-cyano-4,6-bis(methylthio)-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine ( 1 ). Attempts to synthesize 8-amino-6-methyl-2-(β-D-ribofuranosyl)-1H-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene ( 5 ) ([an aza analog of 6-amino-4-methyl-8-(β-D-ribofuranosyl)-1,3,4,5,8-pentaazaacenaphthylene (TCN)], which is a potent antitumor agent), by the treatment of 3 with Raney nickel did not afford the desired aza analog of TCN. Instead, it was established that a reductive cleavage of the pyridazine moiety of 3 had occurred to give 4-methylamino-6-methylthio-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 6 ). Assuming that solubility was a problem in the reductive step, the isopropylidene derivative of 3 , 8-amino-6-methyl-4-methylthio-2-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene ( 8 ), was treated with Raney nickel, only to observe that a similar reductive ring cleavage of 8 had occurred to afford 4-methylamino-6-methylthio-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 10 ) and 4-methylamino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 11 ). Structural assignments for all products were established by physico-chemical procedures.     

Syntheses of 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one,an isostere of oxanosine,and the guanosine analog 6-amino-1-(β-d-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one via ring closure of pyrazole-5-thioureido intermediates

6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 4 ), an isostere of the nucleoside antibiotic oxanosine has been synthesized from ethyl 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxylate ( 6 ). Treatment of 6 with ethoxycarbonyl isothiocyanate in acetone gave the 5-thioureido derivative 7 , which on methylation with methyl iodide afforded ethyl 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-ethoxycarbonyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxylate ( 8 ). Ring closure of 8 under alkaline media furnished 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 10 ), which on deisopropylidenation afforded 4 in good yield. 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 5 ) has also been synthesized from the AICA riboside congener 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxamide ( 12 ). Treatment of 12 with benzoyl isothiocyanate, and subsequent methylation of the reaction product with methyl iodide gave 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-benzoyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxamide ( 15 ). Base mediated cyclization of 15 gave 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 14 ). Deisopropylidenation of 14 with aqueous trifluoroacetic acid afforded 5 in good yield. Compound 4 was devoid of any significant antiviral or antitumor activity in culture.     

Synthesis of 2-(β-D-ribofuranosyl)[1,3,5]triazines

The synthesis of the first [1,3,5]triazine carbon linked nucleosides are reported. 4-Amino-6-(β-D-ribofuranosyl)[1,3,5]triazin-2(1H)-one ( 8 ), an analog of 5-azacytidine and pseudoisocytidine was prepared. 2,5-Anhydro-D-allonamidine hydrochloride ( 3 ) was condensed with dimethyl cyanoiminodithiocarbonate ( 4 ) to give 4-methylthio-6-(β-D-ribofuranosyl)[1,3,5]triazin-2-amine ( 5 ). Compound 5 was reacted with m-chloroperbenzoic acid to give 4-methylsulfinyl-6-(β-D-ribofuranosyl)[1,3,5]triazin-2-amine ( 6 ). Displacement of the methyl sulfinyl with the appropriate nucleophile gave 6-(β-D-ribofuranosyl)[1,3,5]triazine-2,4-diamine ( 7 ), 4-amino-6-(β-D-ribofuranosyl)[1,3,5]triazin-2(1H)-one ( 8 ), and 4-amino-6-(β-D-ribofuranosyl)[1,3,5]triazine-2(1H)-thione ( 9 ). Dethiation of compound 5 with Raney nickel gave 4-(β-D-ribofuranosyl)[1,3,5]triazin-2-amine ( 10 ). The crystal structure of 7 was determined by single crystal X-ray.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Synthesis of N-methylmorpholinium 6-oxo-3,5-dicyano-1,4,5,6-tetrahydro-4-(spirocyclopentane)pyridine-2-thiolate with the Michael reaction

N-Methylmorpholinium 6-oxo-3,5-dicyano-1,4,5,6-tetrahydro-4-(spirocyclopentane)pyridine-2-thiolate was obtained by reaction of cyclopentylidenecyanoacetic ester with cyanothioacetamide or cyclopentylidenecyanothioacetamide with cyanoacetic ester in the presence of N-methylmorpholine; it is used in synthesis of substituted 2-alkylthiotetrahydropyridines, 5-oxo-6,8-dicyano-2,3,6,7-tetrahydro-(5H)-7-(spirocyclopentane)-thiazolo[3,2-a]pyridine, 5-allyl-2-methylthio-3,5-dicyano-4,5-dihydro-4-(spirocyclo-pentane)pyridin-6(1H)-one, and 3-amino-6-oxo-5-cyano-4,5-dihydro-4-(spirocyclopentane)-2H-pyrazolo[5,4-b]pyridin-6(7H)-one. T. G. Shevchenko Lugansk State Pedagogical Institute, Lugansk 348011, Ukraine, N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 117913, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 208–212, February, 1998.     

Reaction of 5-amino-1-aryl-3-methylpyrazoles with benzylidene derivatives of meldrum's acid: Synthesis and characterization of pyrazolo[3,4-b]pyridinones

A series of dihydropyrazolo[3,4-b]pyridin-6-ones 3 was prepared by cyclization of 5-amino-1-aryl-3-methylpyrazoles 1 and Meldrum's acid benzylidene derivatives 2 in nitrobenzene. The structure of 4,5-dihydropyrazolo[3,4-b]pyridin-6-ones and reaction orientation were determined by nmr measurements.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

The synthesis of imidazo[4,5-d]pyridines from a substituted imidazole and acyl or sulfonyl acetonitrile

1-Aryl-5-amino-4-cyanoformimidoyl imidazoles were reacted with acyl and sulfonyl acetonitriles, under mild experimental conditions, leading to imidazo[4,5-b]pyridines and imidazo[4,5-b]pyridine-5-ones. A reaction intermediate could be isolated in the reaction with methyl cyanoacetate, under carefully controlled experimental conditions. This intermediate cyclized to imidazo[4,5-b]pyridine-5-one, in the presence of DBU. Reaction between 5-amino-4-cyanoformimidoyl-1-(4-fluorophenyl)imidazole and acetylacetone, occurred by a different pathway to give a 6-carbamoylpurine.