Synthesis and properties of sym-triazine derivatives. 7. Synthesis of pyridyl-substituted 2-amino- and 2,4-diamino-sym-triazines

N-Substituted 2,4-diamino-6-pyridyl-sym-triazines were synthesized by cyclocondensation of pyridinecarboxylic acid esters with biguanides. 4,6-Disubstituted 2-amino-sym-triazines containing pyridyl residues were obtained by the reaction of pyridinecarboxylic acid nitriles with guanidine or of pyridinecarboxylic acid esters with N-imidoylguanidines. Aminotriazines of this type are also formed in the condensation of N-acylguanidines with nitriles or imino esters. The general principles of the fragmentation of 2-amino-4-dialkylamino-6-pyridyl-sym-triazines under the influence of electron impact were established.See [1] for Communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 674–680, May, 1988.     

Synthesis and properties of azoles and their derivatives. 32. Synthesis and some transformations of hydrochlorides of imido esters of indolecarboxylic acids

The Pinner reaction with the nitriles of indole-3-carboxylic and 3-indolylacetic acids was studied. The hydrochlorides of the imido esters of these acids, which were converted to the free bases, amides, and esters, were synthesized. Imid-azolines, benzimidazoles, and benzoxazoles that contain indole substituents were obtained by condensation of the hydrochlorides of the imido esters of the indolecarboxylic acids with ethylenediamine, o-phenylenediamine, and o-aminophenol.See [1] for communication 31.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 645–650, May, 1980.     

Synthesis and properties of azoles and their derivatives

A method is proposed for the synthesis of 1-(2-cyanoethyl)-2-substituted 2-imidazolines; the method is based on reaction of N-(2-cyanoethyl)ethylenediamine with the hydrochlorides of methyl imino esters of carboxylic acids.See [1] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1674–1675, December, 1973.     

Synthesis of di- and trisubstituted 1,2,4-triazoles containing indole fragments

The reaction of imino esters of indole-series acids with acid hydrazides gave N₍₁₎-acylamidrazones, which, during heating, were converted to 3,5-disubstituted 1H-1,2,4-triazoles containing indole fragments. Compounds of this type were also synthesized by the reaction of indolyl-containing 2,5-disubstituted 1,3,4-oxadiazoles with formamide. Condensation of 2,5-disubstituted 1,3,4-oxadiazoles with aniline gave 3,4,5-trisubstituted 4H-1,2,4-triazoles containing indolyl radicals. Cyclocondensation of N₍₁₎-phenylamidrazones of indole-series acids with benzoyl chloride gave 1,3,5-trisubstituted 1H-1,2,4-triazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 189–196, February, 1993.     

Synthesis of 1,3,5-Trisubstituted 1H-1,2,4-Triazoles Containing Hetaryl Fragments

N¹-Phenyl- and N¹-(3,5-dichloro-2-pyridyl)amidrazones have been synthesized by the reaction of imino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine. Acylation of the products with acid chlorides leads to 1-phenyl- and 1-(3,5-dichloro-2-pyridyl)-3-hetaryl-5-R²-1H-1,2,4-triazoles. Compounds of this type are also formed by the condensation of N-acylimino esters of heterocyclic acids with phenyl- or (3,5-dichloro-2-pyridyl)hydrazine.     

Reaction of 2-dimethylaminomethylene-1,3-diones with dinucleophiles. VIII. Synthesis of ethyl and methyl 2,4-disubstituted 5-pyrimidinecarboxylates

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with N-C-N dinucleophiles such as guanidine, acetamidine or benzamidine afforded in high yields the relative esters of 4-substituted 2-amino-, 2-methyl- or 2-phenyl-5-pyrimidinecarboxylic acids, respectively. These esters were hydrolyzed to the corresponding carboxylic acids, which were converted by heating to 4-substituted 2-pyrimidinamines, 2-methyl or 2-phenylpyrimidines, respectively, generally in excellent yields. The 4-unsubstituted ethyl 2-amino-, 2-methyl- and 2-phenyl-5-pyrimidinecarboxylates were obtained in moderate yields by reaction of the above dinucleophiles with ethyl 2,2-diformylacetate. These esters were hydrolyzed and the corresponding acids (with the exception of the 2-methyl derivative) were decarboxylated to give 2-pyrimidinamine and 2-phenylpyrimidine in satisfactory yields.     

Synthesis and properties of derivatives of sym-triazines. 11. Synthesis of 2-amino-sym-triazines containing alkyl radicals

2-Amino-4,6-dialkyl-sym-triazenes were synthesized by the condensation of aliphatic nitriles with guanidine. 2-Amino-4-alkyl-6-substituted sym-triazines were prepared by the reaction of N-acylguanidines with nitriles or imino esters. Aminotriazines of this type are also formed in the condensation of N-imidoylguanidines with esters.For Communication 10, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1271–1276, September, 1993.     

Synthesis of methyl -substituted 4-amino methyl-4-butanolides and 5 -hydroxy-2-piperidones

Esters of 5-amino-4-hydroxy-3-methylvaleric acids, which exist as pairs of diastereomers and are readily converted to the corresponding methyl-substituted 4-aminomethyl-4-butanolides or 5-hydroxy-2-piperidones, are obtained by reaction of esters of 3-methyl-4, 5-epoxy-2-pentenoic acid with amines and subsequent hydrogenation of the resulting esters of 5-amino-4-hydroxy-3-methyl-2-pentenoic acids.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 594–598, May, 1975.     

Chemistry of iminofuran: VIII. Recyclization of 5-aryl-3-arylimino-3H-furan-2-ones effected by cyanoacetic acid derivatives

The recyclization of 5-aryl-3-arylimino-3H-furan-2-ones under the action of esters, nitriles, and amides of cycnoacetic acids resulted in the corresponding esters, nitriles, and amides of (5E)-2-amino-1-aryl-4-oxo-5-(2-oxoethylidene)-1H-4,5-dihydropyrrole-3-carboxylic acids.     

Synthesis of heterocycles from products of the anion arylation of unsaturated compounds. 3. 2-arylimino-5-arylmethyl-4-thiazolidones

The reaction of esters of 3-aryl-2-bromopropionic acids with N-arylthioureas gives 2-arylimino-5-arylmethyl-4-thiazolidones, which exist in solution as (E) and (Z) isomers of the imino form.For Communication 2, see [1].I. Franko Lvov State University, Lvov 290602, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 555–559, April, 1998.     

Fluorinated aminooxazolines. Synthesis and properties

4-Amino-2,2,5,5-tetrakis(trifluoromethyl)-3-oxazoline ( 3a ) was prepared from the reaction of sodium cyanide with hexafluoroacetone and hexafluoroacetone imine, and from the reaction of hexafluoroacetone cyanohydrin with the imine. Several other oxazolines were also prepared by related reactions of other fluoroketones and imines. The proton nmr spectrum of an ¹⁵N-labeled sample of 3a shows that it exists in solution primarily as the amino tautomer and not as the imino tautomer 3b . Comparison of 3a with the closely related, pharmacologically active 4-amino-2,2,5,5-tetrakis(trifluoromethyl)-3-imidazoline ( 2 ) has shown large differences in ΔH of complex formation and reactivity with electrophilic reagents.     

Acid cyclization of amino-substituted heterocycles. Synthesis of 1,3-dioxo- pyrrolo[3,4-<Emphasis Type="Italic">c</Emphasis>]- and thieno[3,4-<Emphasis Type="Italic">c</Emphasis>]isoquino- lines and cinnolines

The reaction of 3-amino-4-(3,4-dimethoxyphenyl)maleimide and the methyl esters of 3-amino-4-(3,4-dimethoxyphenyl)-5-R-thiophene-2-carboxylic acids with carbonyl compounds and nitrous acid has been investigated. Dioxopyrrolo[3,4-c]- and thieno[3,4-c]isoquinolines and cinnolines were obtained. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 449-454, March, 2009.     

Synthesis and glutamate-agonistic activity of (S)-2-amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)-propanoic acid derivatives.

(S)-2-Amino-3-(2,5-dihydro-5-oxo-3-isoxazolyl)propanoic acid, (3a) and its analogs (3b--h) were prepared and evaluated for glutamate receptor-agonistic and antifungal activities. Several (S)- and (R)-2-amino-3-isoxazolylpropanoic acid derivatives (3a--d) were synthesized starting with (S)- and (R)-N-tert-butoxycarbonyaspartic acid alpha-methyl esters (4, n = 1) by means of Masamune's chain extension reaction followed by isoxazolone formation with hydroxylamine and subsequent deprotection reactions. Furthermore, (S)- and (R)-N-tert-butoxycarbonylglutamic acid alpha-methyl esters (4, n = 2) were converted to (S)- and (R)-2-amino-4-isoxazolylbutyric acid derivatives (3e-h) via the same sequence of reactions.     

Synthesis and reduction of esters of N-(4-amino-5-nitro-6-pyrimidyl)amino acids

The reaction of esters of amino acids with 4-amino-6-chloro-5-nitropyrimidine has yielded esters of (4-amino-5-nitro-6-pyrimidyl)amino acids. The reduction of the esters of -(4-amino-5-nitro-6-pyrimidylamino) acids has yielded 4-amino-6-hydroxy-7,8-dihydropteridines. -(4-Amino-5-nitro-6-pyrimidylamino) acids and the ester of N-(4-amino-5-nitro-6-pyrimidyl)--alanine do not cyclize and on reduction give the corresponding diaminopyrimidine derivatives.     

Synthesis of trifluoromethyl derivatives of alkyl 2-nitromethylphosphonopropionates and -phosphonobutyrates

By adding diethyl hydrogen phosphite to 5-trifluoromethyl-2-furaldehyde (5-trifluoromethylfur-2-yl)(diethoxyphosphoryl)methanol was synthesized. It was oxidized with DMSO-acetic anhydride mixture to diethyl 5-trifluoromethyl-2-furoyl phosphonate. The reaction of the latter with ethoxymethylenetriphenylphosphorane gives ethyl (2E)-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propenoate. Analogous reaction of (diethoxyphosphoryl)(5-trifluoromethylfur-2-yl)acetic aldehyde yields ethyl (4E)-4-(diethoxyphosphoryl)-4-(5-trifluoromethylfur-2-yl)-but-3-enoate. The addition of nitromethane to these esters of unsaturated acids in the presence of potassium fluoride gives a mixture of diastereomers of phosphorylated esters of 2-nitromethyl-3-(5-trifluoromethylfur-2-yl)propanoic and 3-nitromethyl-4-(5-trifluoromethylfur-2-yl)butanoic acids respectively. By the reduction of ethyl nitropropanoate with zinc and formic acid in dioxane ethyl 2-aminomethyl-3-(diethoxyphosphoryl)-3-(5-trifluoromethylfur-2-yl)propanoate was prepared in a low yield. It may be considered as the derivative of β-alanine containing additional pharmacophore fragments.     

Synthesis and properties ofsym-triazene derivatives 13. Synthesis of 6-substituted 2,4-dialkyl(aryl)thio-sym-triazenes from imino esters of carboxylic acids

6-Substituted 2,4-dialkyl(aryl)thio-sym-triazenes are synthesized by condensation of imino esters of carboxylic acids with thiocyanates.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1125-1128, August, 1994.For paper 12, see [1].     

Synthesis of alkyl-substituted 2-halo-4-aminomethyl-2-buten-4-olides

The reaction of esters of alkyl-substituted (E)-5-amino-4-hydroxy-2,3,epoxyvaleric acids with some hydrohalic acids gave the corresponding 2-halo-4-amino-methyl-2-buten-4-olides, the hydrochlorides of which have diuretic activity.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1471–1474, November, 1985.     

Synthesis of imidazolino [1,2-f]xanthin-2-ones and their methylene-group-substituted derivatives

8-Amino-7-theophyllylacetic acids and their esters were obtained by reaction of 8-amino(alkylamino, arylamino)theophyllines with haloacetic acids and their esters. The structures of the products were established, and the conditions for cyclization to imidazolino[1,2-f]xanthin-2-one derivatives were studied. The corresponding methylene-group-substituted derivatives were synthesized by reaction of the imidazolino[1,2-f]xanthin-2-one derivatives with aldehydes, isatin, aromatic nitroso compounds, and arenediazonium salts. The ylidene derivatives of this threering system were also obtained by reaction of 8-amino-7-theophyllylacetic acids or their esters with carbonyl compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1132–1135, August, 1976.     

Synthesis of some sym-triazole derivatives

3,5-Di(hydroxyalkyl) derivatives of 4-amino-1,2,4-triazole and the corresponding derivatives of 1,2,4-triazole obtained by diazotizing them are converted by reaction with SOCl₂ into the hydrochlorides of 4-amino-3,5-di(chloroalkyl)-1,2,4-triazoles and 3,5-di(chloroalkyl)-1, 2,4-triazoles. The dinitrate of 3,5-di(hydroxymethyl)-1,2,4-triazole has been prepared. When the cyanohydrazide of glycolic acid is heated with hydrazine hydrate, 4,5-diamino-3-hydroxymethyl-1, 2,4-triazole is formed.     

Synthesis of new 3<Emphasis Type="Italic">H</Emphasis>-pyrrole derivatives from 3-aryl-2-oxa-7-azaspiro[4.4]nona-3,6,8-trienes

8-Amino-3-aryl-1-imino-4-methyl-6-(morpholin-4-yl)-2-oxa-7-azaspiro[4.4]nona-3,6,8-triene-9-carbonitriles reacted with acetic anhydride to give different products, depending on the solvent. The reaction in tetrahydrofuran gave the corresponding N-acyl derivatives at the imino group, whereas in pyridine 5-amino-2-morpholin-4-yl-3-(1-aryl-1-oxopropan-2-yl)-3H-pyrrole-3,4-dicarbonitriles were formed as a result of opening of the furan ring.