Azaindole derivatives. 57. Dehydrogenation of substituted 5- and 7-az aindolines with activated manganese dioxide

A number of 5- and 7-azaindolines were oxidized to the corresponding azaindoles by means of activated manganese dioxide. The dependence of the ease of dehydrogenation of 5- and 7-azaindolines by activated manganese dioxide on their oxidation potentials is demonstrated.See [1] for communication 56.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 375–378, March, 1979.     

Pyrido[2,3-d]dipyrimidines 8. Synthesis of pyrrolo(2′,3′∶4,5)pyrido[2,3-d]pyrimidines

The reaction of 1,3-dimethyl-5-chloro-6-nitropyrido[2,3-d]pyrimidine-2,4-dione with CH-acids yielded 5-substituted pyridol[2,3-d]pyrimidines which were used in the synthesis of pyrrolo(2,34,5)pyrido[2,3-d]pyrimidines.For Communication 7, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 800–803, June, 1993.     

Synthesis of methyl esters of 5-amino-4-(substituted amino)-2-methylthio-7H-pyrrolo[2,3d]-pyrimidine-6-carboxylic acids

The optimum route for the synthesis of methyl esters of N-[(4-substituted amino)-5-cyano-2-methylthiopyrimidin-6-yl]amino acids (which are starting materials for preparing the methyl esters of the corresponding 5-amino-4-(substituted amino)pyrrolo[2,3-d]pyrimidine-6-carboxylic acids) is via subsequent reactions of 4,6-dichloro-2-methylthiopyrimidine-5-carbonitrile with amines and methyl glycinate. In some examples, the reaction of methyl N-(4-chloro-2-methylthio-6-pyrimidinyl)aminoacetate with amines occurs to give the corresponding acid amides. The previously unknown synthesized derivatives of pyrimidin-6-yl amino acids and 4,5-diaminopyrrolo[2,3-d]pyrimidine- 6-carboxylic acids possess fungicidal properties.Vilnius University, Vilnius 2006, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 7, pp. 955–961, July, 2000.     

Derivatives of orotic acid and its analogs

The synthesis of oxo derivatives of pyrrolo[3, 4-d]pyrimidine has been effected by the reaction of the lactone of 5-(hydroxymethyl)-orotic acid with ammonia or primary amines. In a number of cases, in place of the free organic bases their salts with mineral acids were used successfully. A number of 2, 4, 7-trioxo derivatives of pyrrolo[3, 4-d]pyrimidine and some new derivatives of orotic acid have been synthesized.     

Synthesis and unusual chemical reactivity of certain novel 4,5-disubstituted 7-benzylpyrrolo[2,3-d][1,2,3]triazines.

The fact that only two pyrrolo[2,3-d][1,2,3]triazines heterocycles had been reported in the literature prompted us to initiate studies designed to provide additional members of this ring system. Initial attempts to prepare additional derivatives of the 7-unsubstituted pyrrolo[2,3-d][1,2,3]triazin-4-ones were limited by their low chemical reactivity. Subsequently, 7-benzyl-5-carboxamidopyrrolo[2,3-d][1,2,3]triazin-4-one (16) was prepared from diethyl 2-nitropyrrole-3,4,-dicarboxylate via an alkylation, ammonolysis, reduction and intramolecular diazocoupling sequence. Conversion of 16 into 7-benzyl-4-(1,2,4-triazol-1-yl)pyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (17) was accomplished, and nucleophilic displacements of the 4-triazol-1-yl group were studied. Treatment of 17 with NH3/CH3CN gave a mixture of 4-amino-7-benzylpyrrolo[2,3-d][1,2,3]triazine-5-carbonitrile (19) and 2-amino-1-benzylpyrrole-3,4-dicarbonitrile (21). A mechanism to account for the formation of this mixture is described along with studies on the effect that ammonia concentration and a TFA catalyst have on the product ratio. Compound 19 was converted into the 5-carboxamide and 5-thioamide derivatives of 19.     

Acetals of lactams and acid amides. 40. Synthesis and hydrolytic cleavage of one-ring and two-ring derivatives of 4-pyrimidinone

The reaction of 1-benzyl-5-cyano-6-dimethylaminomethylene-1, 6-dihydro-4-pyrimidinone with acid leads to 5-benzyl-1,2,7,8-tetrahydropyrido[4,3-d]pyrimidine-1,8-dione, whereas the reaction with ammonia leads to a mixture of 3-cyano-4-benzylamino-2-pyridone and 1-amino-5-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. Heating of the latter in aqueous ethylene glycol is accompanied by recyclization to give 4-benzylamino-5,6-dihydropyrido[2,3-d]pyrimidin-5-one. The reaction of 1-benzyl-4-ditnethylaminomethylene-5-cyano-1,6-dihydro-6-pyrimidinone with ammonia leads to 1-amino-7-benzyl-7,8-dihydropyrido[4,3-d]-pyrimidin-8-one. The rate constants for cleavage of the pyrimidine ring in a number of 4-pyrimidinone derivatives were measured.See [1] for communication 39.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 532–537, April, 1984.     

Azaindole derivatives

The polarographic oxidation of a series of 5-azaindoline, 7-azaindoline, and 5,7-diazaindoline derivatives (22 compounds) was studied, and the results are compared with the ease of dehydrogenation of these substances under the influence of quinones. It is shown that E_1/2 increases on passing from 7-azaindolines to 5-azaindolines and then to 5,7-diazaindolines. The effect of substituents is satisfactorily described by cross-correlation equations, while the deviations from the correlation are associated with the peculiarities of the lactam-lactim tautomeric equilibrium in a number of 6-hydroxy-5- and 7-azaindolines.See [1] for communication XLI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 773–776, June, 1973.     

Pyrimidine derivatives. 57. New method for the synthesis of pyrrolo[2,3-d]pyrimidine

The action of bromine on 5-allyl-6-aminopyrimidines was studied. The formation of both a product of addition of bromine to the allylic bond and pyrrolo [2,3-d]-pyrimidines is possible, depending on the character of the substituent attached to the amino group. The structures of the synthesized compounds were confirmed by PMR and mass-spectrometric data.See [1] for Commication 56.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1686–1689, December, 1982.     

Reactions of heterocyclic cations with n-containing nucleophiles. 15. Reaction of 2,6-diphenylpyrylium perchlorate with semi- and thiosemicarbazides

The reaction of 2,6-diphenylpyrylium perchlorate with semi- and thiosemicarbazides in ethanol leads to 1-carbamoyl- and 1-thiocarbamoyl-3-phenyl-5-phenacyl-4,5-dihydropyrazoles, the cyclization of which yields 2,5-diphenyl-7-oxo(thio)-pyrazolo[1,5-c]pyrimidines. The tautomeric form of the latter is established by comparing their electronic absorption spectra with the spectra of the methyl derivatives.For Communication 14, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1635–1640, December, 1986.     

Azaindole derivatives

The reaction of 6-chloro-7-azaindolines with naphthyllithium and subsequent treatment with benzophenone give (7-aza-6-indolinyl)diphenylcarbinol and 6-unsubstituted 7-azaindolines, the ratios of the amounts of which are determined by the character of the substituent attached to the nitrogen atom in the 1 position of the azaindoline molecules. In the presence of acidic catalysts (1-butyl-4-methyl-7-aza-6-indolinyl)diphenylcarbinol undergoes dehydration to 1-butyl-4-methyl-6-diphenylmethyl-7-azaindole. Ideas regarding the mechanism of this reaction are expressed.See [1] for communication L.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1527–1530, November, 1977.The authors thank Yu. N. Sheinker, K. F. Turchin, L. F. Linberg, E. M. Peresleni, and T. Ya. Filipenko for conducting the spectral investigations.     

Azaindole derivatives

In addition to normal nucleophilic substitution, redox processes to form dehalogenation products of 7-azaindoline and the corresponding oxidized compounds — 6-amino-7-azaindole derivatives — occur during the reactions of various primary and secondary amines with 6-chloro-7-azaindolines. The quantitative ratios of the products of nucleophilic substitution and the redox reaction depend mainly on the nucleophilicity of the attacking amine and, by selecting the amine component of the reaction, one can accomplish either predominantly nucleophilic substitution or direct the process primarily along the path of the redox reaction.See [1] for communication XXXVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 789–794, June, 1971.     

Study of Nitrogen- and Sulfur-Containing Heterocycles. 57. Synthesis and Conversion of 4′-Substituted 5-(5-Amino-6-Pyrimidylthio)-2,2-Dimethyl-4,6-Dioxo-1,3-Dioxanes

By reaction of 4-substituted 5-amino-6-mercaptopyrimidines with 5-bromo-2,2-dimethyl-4,6-dioxo-1,3-dioxane, we have obtained 4′-substituted 5-(5-amino-6-pyrimidylthio)-2,2-dimethyl-4,6-dioxo-1,3-dioxanes. We have studied diazotization of these compounds by isoamyl nitrite. In the case of 4′-methoxy- and 4′-dimethylamino-substituted derivatives, we have obtained derivatives of novel heterocyclic systems: pyrimido[5,4-e][1,3,4]thiadiazine and pyrimido[5,4-e][1,3,4]thiadiazine-7-spiro-5′-1,3-dioxane, and in the case of the 4′-isopropylamino-substituted derivative we obtained 4-isopropyl-7-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-1,2,3-triazolo[5,4-d]pyrimidin-7-ylidene.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 613–623, April, 2005.     

Deazapurine solid-phase synthesis: combinatorial synthesis of a library of N3,N5,C6-trisubstituted pyrrolo[3,2-d]pyrimidine derivatives on cross-linked polystyrene bearing a cysteamine linker

Solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidine-6-carboxylates with diversity at the N3 pyrmidine nitrogen has now been elaborated to allow for the generation of pyrrolopyrimidine libraries with members possessing diversity at the N3, N5, and C6 positions. The diversification of the N5 position was achieved by treating the parent resin-bound pyrrolo[3,2-d]pyrimidines 3 with an alkyl halide in the presence of Cs2CO3 in DMF. Modification of the C6 carboxylate of resin-bound pyrrolopyrimidines 3-5 was first achieved by hydrolysis of the benzyl ester using LiOH in a mixture of THF/H2O/MeOH. Further alteration of the C6 position of resin-bound pyrrolo[3,2-d]pyrimidine-6-carboxylic acids 6-8 was then performed by activation with triphosgene and treatment with an amine to furnish resin-bound pyrrolo[3,2-d]pyrimidine-6-amides. Twenty-two pyrrolo[3,2-d]pyrimidines 1a-v with different substituents at the N3, N5, and C6 positions were obtained in yields of 21-83% and purities of 61-98% after cleavage from the solid support.     

Research in the imidazole series

The reduction of pyrrolo[1,2-a]imidazole-2-one and pyrrolo[1,2-a]benzimidazole derivatives, which leads to the formation of 2,3-dihydropyrrolo[1,2-a]imidazole derivatives and derivatives of the previously unknown 1,2,3,3a-tetrahydropyrrolo[1,2-a]benzimidazole, was studied. A method was developed for the preparation of 5- and 7-amino derivatives of pyrrolo[1,2-a]imidazole by reduction of the corresponding nitroso- and arylazo-substituted pyrrolo[1,2-a]-imidazoles.See [1] for communication XCI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 225–228, February, 1977.     

Reaction of nitrilimines with 2-substituted aza-heterocycles. Synthesis of pyrrolo[1,2-a]pyridine and pyrimido[2,1-d]1,2,3,5- tetrazine

The reaction of nitrilimine 6a with ethyl pyridine-2-acetate (7) gave the corresponding pyrrolo[1,2-a]pyridine 8, while the reaction of 6b containing an ester moiety afforded the acyclic adduct 9. The reaction of 6a with 2-aminopyrimidine (10) gave the novel unexpected pyrimido[2,1-d]1,2,3,5-tetrazine 11. Acyclic adducts 16 and 17 were obtained from the reaction of 6b with 2-cyanomethylbenzimidazole (14) and 2-aminobenzimidazole (15), respectively.     

Acetals of lactams and acid amides

7-Dimethylamino-5-hydroxypyrido[2,3-d]pyrimidine and pyrrolo-, pyrido, and azepino [2,3-b]pyrido[2,3-d]pyrimidine derivatives were synthesized by reaction of acetals of amides and lactams with 4-amino-5-carbethoxypyrimidine derivatives and subsequent intramolecular cyclization of the intermediate amidines. The reactions of these compounds with phosphorus oxychloride and their alkylation reactions were studied.See [1] for communication XXVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1549–1554, November, 1978.     

Lactam and acid amide acetals 68. 1-Cyanomethyl-2-pyrrolidone diethylacetal in the synthesis of 7,8-trimethylenepurine derivatives

1-Cyanomethyl-2-cyaniminopyrrolidine was synthesized by the reaction of 1-cyanomethyl-2-pyrrolidone diethylacetal with cyanamide. The product undergoes Thorpe—Ziegler cyclization under the influence of sodium ethoxide to give 2-amino-3-cyano-5,6-dihydro-7H-pyrrolo[1,2-a]imidazole, from which 4-amino derivatives of pyrrolo[2,1-f]purine were synthesized.See [1] for Communication 67.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 754–758, June, 1991.     

Investigations in the imidazole series LXXIV. Electrophilic substitution reactions in the pyrrolo[1,2-a]imidazole series

The formylation, acetylation, hydroxymethylation, azo coupling, nitrosation, nitration, and chloromercuration of pyrrolo[1,2-a]imidazole derivatives were studied. The PMR spectra were used to establish that all of these reactions proceed at the 5 position or, if it is occupied, at the 7 position of the two-ring system. When the 5 and 7 positions are free, the formation of 5,7-disubstituted pyrrolo[1,2-a]imidazoles is possible.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 405–409, March, 1972.     

11H-Pyrido[3',2':4,5]pyrrolo[2,3-g]isoquinoléines (aza-7 ellipticines) substituées sur leur position 6

6-Dialkylaminoalkylamino substituted 11H-pyrido[3',2':4,5]pyrrolo[2,3-g]isoquinolines (7-aza ellipti-cines) were obtained by a six step synthesis starting from 2-chloro-3-nitro pyridine and 6-amino-5-methyl (and 5,8-dimethyl) isoquinoline-1-2H-ones already described. A brief survey of biological results shows that derivatives of this new heterocyclic ring system are less interesting than their 5H-pyrido(3',4':4,5]pyrrolo[2,3-g]isoquinolines (9-aza ellipticines) and pyrido[4,3-b]carbazoles (ellipticines) analogues.     

Heterocyclic Quinones in the Nenitzescu Reaction. Synthesis of Furo- and Pyrrolobenzothiazoles from 2-Methyl-4,7-dioxobenzothiazole

Treatment of the enamines of acetylacetone and benzoylacetone with 2-methyl-4,7-dioxobenzothiazole under Nenitzescu reaction conditions gave furo[2,3-e]benzothiazoles (in acetic acid) and pyrrolo[2,3-e]benzothiazoles (in nitromethane). Using enamines of acetoacetic ester gave exclusively pyrrolo[2,3-e]benzothiazoles.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 252–258, February, 2005.