Reactions of 3-methyl-1-(2-pyridyl)-4-chloro-5-formyl-6,7-dihydroindazole

The reactions of 3-methyl-1-(2-pyridyl)-, 3-methyl-1-phenyl-, and 3-methyl-1,6-diphenyl-4-chloro-5-formyl-6,7-dihydroindazoles with guanidine and benzo- and 3- and 4-pyridinecarbamidines gave the corresponding 8-substituted 1-methyl-3-(2-pyridyl)-and 1-methyl-3-phenyl-4,5-dihydropyrazolo[5,4-h]quinazolines. With acetic anhydride the same indazole derivatives gave the 4-acetoxy-5-formyl derivatives, and with hydroxylamine they gave4-chloro-5-hydroxyiminomethyl-6,7-dihydroindazoles. Thereactionof4-acetoxyl-1-(2-pyridyl)-5-formyl-6,7-dihydroindazole with hydroxylamine gave 8-methyl-6-(2-pyridyl)-4,5-dihydroisoxazolo[5,4-e]indazole, while dehydration of 5-hydroxyiminomethyl-3-methyl-4-chloro-6,7-dihydroindazole gave the 4-chloro-5-cyano derivative. The reaction of the latter with nucleophilic reagents was investigated.Riga Technical University, Riga, Latvia LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1209–1213, September, 1998.     

Reactions of 2-Amino-4-methyl-6-(2-pyridyl)- and 2-Amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazoles with Aldehydes

The reaction of 2-amino-4-methyl-6-(2-pyridyl)-7,8-dihydroindazolo[4,5-d]thiazole, obtained by treating 3-methyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole with pyridinium bromide perbromide and then with thiourea, and 2-amino-4-methyl-6-phenyl-7,8-dihydroindazolo[4,5-d]thiazole with 4-bromo-, 4-fluoro-, 4-dimethylamino-, 4-methoxy-, 3,4-dimethoxy-, and 3,4-methylenedioxybenzaldehydes, furfural, pyridinecarbaldehyde, and thiophenecarbaldehyde gave the corresponding Schiff bases. The products of the condensation of these aminothiazoles with cinnamaldehyde, 1-(2-pyridyl)- and 4-chloro-1-(2,4-difluorophenyl)-5-formyl-3-methyl-6,7-dihydroindazoles, 2-formyl-dimedone, and 2-formyl-1,3-indanedione were also obtained.     

4,5-Dihydropyrazolo[3,4-f]quinazolines

By reaction of 6-dimethylamino-5-oxo-2-phenyl-5,6,7,8-tetrahydroquinazoline with hydrazine, phenylhydrazine, 4-bromo-, 4-chlorophenylhydrazines, and also reaction of 6-dimethylaminomethylene-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazoline with hydrazine, 4-methoxy- and 2-carboxyphenylhydrazines, we have obtained the corresponding 7-phenyl(4-pyridyl)-substituted 1H(2H)- or 1-aryl-4,5-dihydropyrazolo[3,4-f]quinazolines. Methylation of 7-phenyl-4,5-dihydro-1(2H)-pyrazolo[3,4-f]quinazoline by methyl iodide led to its 2-methyl derivative.     

Cycloaddition reactions of cyclic ketene-N,S-acetals with 1,2,4,5-tetrazines

Reaction of 3,6-diphenyl-, 3,6-bis(2-pyridyl)- and the unsubstituted 1,2,4,5-tetrazine with 4,5-dihydro-1-methyl-2-(methylthio)pyrrole ( 2 ) and 1-raethyl-2-(methylthio)-4.5,6,7-tetrahydroazepine ( 3 ) gives 4,7-di-R-2,3-dihydro-1-methylpyrrolo[2,3-d]pyridazine ( 4 , R = phenyl, 2-pyridyl, hydrogen) and 6,9-di-R-1-methyl-2,3,4,5-tetrahydropyridazino[4,5-6]azepine ( 5 ), R = phenyl, 2-pyridyl, hydrogen), respectively, in reasonable to good yields. The compounds 4 (R = phenyl, hydrogen) are converted into their corresponding 1-methylpyrrolo-[2,3-d]pyridazines 6 by reaction with potassium permanganate in butanone. Reaction of 3-phenyl-1,2,4,5-te-trazine with 2 and 3 leads to the exclusive formation of the 7-phenyl isomer 4d and 9-phenyl isomer 5d , respectively, indicating that the cycloaddition is regiospecific. The mechanism is discussed.     

Derivatives of 1-(2-pyridyl)-4,5,6,7-tetrahydroindazole

In reaction of oxidation of 1-(2-pyridyl)3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindazole, the corresponding 4,5-dioxoindazole is obtained, and then 1-(2-pyridyl)-3-methyl-4-carboxy-5-(2-methyl-2-carboxypropyl)pyrazole; in bromination reaction, a series of 5-bromo and 7-bromo derivatives is obtained. From 4,5-dioxoindazole with hydrazides of acids, a series of 4-oxo-5-acylhydrazono derivatives is obtained, and also 1-(2-pyridyl)-3,6,6-trimethyl-4-oxo-5-tosylhydroindazole, which, under the action of caustic, gives the 4-oxo-5-diazo derivative.Riga Technical University, Riga LV-1658. Translated from Khimiya Geterotsiklicheskikh Soerdinenii, No. 3, pp. 351–354, March, 1995. Original article submitted December 29, 1994.     

3,6,6-trimethyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole in Schmidt reaction and Beckmann rearrangement conditions for the 4-hydroxyimino derivative

Treatment of 3,6,6-trimethyl-4-oxo-1-(2-pyridyl)-4,5,6,7-tetrahydroindazole with sodium azide in acids gives 3,7,7-trimethyl-5-oxo-1-(2-pyridyl)-5,6,7,8-tetrahydro(4H)pyrazolo[4,3-b]azepine. Heating 1-(2-pyridyl)-3,6,6-trimethyl- and 1-phenyl-6,6-dimethyl-4-hydroxyimino-4,5,6,7-tetrahydroindazoles in polyphosphoric acid gives 1-phenyl-5,6-dimethyl- and 1-(2-pyridyl)-3,5,6-trimethyl-4-aminoindazole respectively: The reactions of the latter with 4-dimethylaminobenzaldehyde gave the 4-(4-dimethylaminobenzalamino) derivative and with 2-formyldimedone the 4-(4,4-dimethyl-2,6-dioxocyclohexylidenemethylamino) derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 830–834, June, 2000.     

4-(10-Methyl-10H-phenothiazin-3-yl)-1,4-dihydropyridines, 4,5-dihydroindeno[1,2-<Emphasis Type="Italic">b</Emphasis>]-and 5,5-dioxo-4,5-dihydrobenzo-thieno[3,2-<Emphasis Type="Italic">b</Emphasis>]pyridines

Different modifications of the Hantzsch synthesis using 10-methyl-10H-phenothiazine-3-carbaldehyde gave 4-(10-methyl-10H-phenothiazin-3-yl)-substituted 1,4-dihydropyridine-3,5-di-, 5-oxo-4,5-dihydro-1H-indeno[1,2-b]pyridine-, and 5,5-dioxo-4,5-dihydro-1H-5λ⁶-benzo[4,5]thieno[3,2-b]pyridine-3-carboxylic esters. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–288, February, 2007.     

Pyridyl-substituted [1,3]Dithiolo-[4,5-<Emphasis Type="Italic">b</Emphasis>][1,4]dithiine-2-thiones

We have obtained 5-(2-pyridyl)[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione for the first time by cycloaddition of 2-ethynylpyridine to 4,5-dihydro-1,3-dithioltrithione (isotrithionedithiol). We have studied this thione, 5-(2-pyridyl)- and 5-(4-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thiones by mass spectroscopy and also IR, UV, ¹H and ¹³C NMR spectra. We have determined the crystal and molecular structure of 5-(2-pyridyl)-5,6-dihydro[1,3]dithiolo[4,5-b][1,4]dithiine-2-thione.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 429–434, March, 2005.     

Synthesis and reactions of 1-(2-pyridyl)-3-methyl-4-chloro-5-formyl-6,7-dihydroindazoles

The Vilsmeier formylation of 1-(2-pyridyl)-3-methyl-4-oxo-4,5,6,7-tetrahydroindazole and its 6-phenyl derivative gives 1-(2-pyridyl)-3-methyl-4-chloro-5-formyl-6,7-dihydroindazoles. Reactions of these derivatives with different N- and C-nucleophilic agents, including bisnucleophiles, were studied as a means of obtaining new 4- and 5-functional derivatives of indazole and its condensed systems.Riga Technical University, Riga LV-1658, Latvia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 768–773, June, 1998.     

Pyrimido[4,5-f]quinazolines

The corresponding 6-dimethylaminomethylen-5-oxo-5,6,7,8-tetrahydroquinazolines were obtained from reactions of 2-substituted and 2,7-disubstituted 5-oxo-5,6,7,8-tetrahydroquinazolines with the dimethylacetal of DMF. Sixteen 2,8-disubstituted 5,6-dihydropyrimido[4,5-f]quinazolines were obtained from the reaction of 2-phenyl- and 6-(dimethylamino)methylen-5-oxo-2-(4-pyridyl)-5,6,7,8-tetrahydroquinazolines with guanidine and eight amidines. The corresponding 6-hydroxymethylene derivative was obtained by hydrolysis of 6-(dimethylamino)methylen-5-oxo-1-phenyl-5,6,7,8-tetrahydroquinazoline.     

Synthesis of several heteryldehydropeptides by the oxazolone method

(E)-N-Benzolydehydro-3-(3-pyridyl)-alanyltryptophan was synthesized in 89% yield by the reaction of 2-phenyl-4-(3-pyridylidene)-5(4H)-oxazolone with tryptophan. The reaction of 4-[1-(2-furyliden)ethyl]- and 4-(3-pyridyliden)2-phenyl-5(4H)-oxazolones with alanyltryptophan gives a mixture of theZ andE isomers of the corresponding dehydrotripeptides. Racemization of the alanyl and tryptophan residues was not observed.Latvian Institute of Organic Synthesis, LV-1006, Riga, Latvia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 232–235, February, 1995. Original article submitted December 24, 1994.     

Synthesis of alkyl thioethers of pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidine

Reaction of 4-imino-1-methyl-5-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine-6-thione with unsaturated alkyl halides gives 4-imino-6-methallylthio(cinnamylthio, allylthio)-1-methyl-5-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidines.     

Reaction of diketene with cyanothioacetamide: A convenient and regioselective method for the preparation of new 4(1H)-pyridone derivatives

The reaction of diketene with cyanothioacetamide in dry dioxane in the presence of triethylamine gives triethylammonium 3-cyano-6-methyl-4-oxo-1,4-dihydro-2-pyridinethiolate. The regioselective S-alkylation of this thiolate is a convenient method for the preparation of substituted 4(1H)-pyridones and also derivatives of thiazolo[3,2-a]pyridine and thieno[2,3-b]pyridine. The action of 2-amino-1,1,3-tricyanopropene on this thiolate leads to its transformation into a new heterocyclic system, namely, 5H-pyrido[2′,3′:4,5]thiopyrano[2,3-b]pyridine; treatment with iodine yields the oxidation product, namely, the corresponding bis(2-pyridyl) disulfide. The structure of isopropyl (3-cyano-6-methyl-4-oxo-1,4-dihydro-2-pyridinyl)thioacetate was confirmed by X-ray diffraction structural analysis. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 716–725, May, 2007.     

Synthesis of pyrido[1,2-a]pyrimido[4,5-d]pyrimidin-5-ones. Cyclization reaction of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid with acetic anhydride

Treatment of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid (X) with acetic anhydride under refluxing conditions afforded 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]-pyrimido[4,5-d]pyrimidin-5-one acetate (IX). The intermediate X was prepared from 4-chloro-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (V). The reaction of V with the sodium salt of 2-amino-3-hydroxypyridine at room temperature gave 4-(2-amino-3-pyridyloxy)-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester (VI). Treatment of VI with a hot aqueous sodium hydroxide solution and subsequent acidification gave X. Involvement of 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecaroboxylic acid ethyl ester (VIII) (Smiles rearrangement product) as an intermediate in the above alkaline hydrolysis reaction of VI to X was demonstrated by the isolation of VIII and its subsequent conversion into X under alkaline hydrolysis conditions. Acetylation of VIII with acetic anhydride in pyridine solution gave 4-[(3-hydroxy-2-pyridyl)amino]-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester acetate (XI), which afforded IX on fusion at 220°. This alternative synthesis of IX from XI supported the structural assignment of IX. Fusion of VI gave 10-hydroxy-2-phenyl-5H-pyrido[1,2-a]pyrimido]4,5-d]pyrimidin-5-one (VII). The latter was also obtained when VIII was fused at 210°. Acetylation of VII with acetic anhydride afforded IX.     

Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of <Emphasis Type="Italic">endo</Emphasis>-ethenotetrahydrothebaine and their behavior in the heck reaction

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C⁷-C⁸ bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.     

Synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3-e][1,6]naphthyridine-8-ones via Pictet–Spengler cyclization

An efficient method for the synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet–Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe–Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF_3·OEt_2 gives pyrimidothieno[1,6]naphthyridines in good yields.     

Chemistry of 6 -pyrido[4,3- ]carbazoles part II: synthetic approaches to 6 -9-methoxy-5, 11-dimethylpyrido[4,3- ] fluorenes

Synthetic approaches to 6 -9-methoxy-5, 11-dimethylpyrido[4,3- ] fluorene are described, thus 2-[1-(4-pyridyl)ethyl]6-methoxyindanone has been reacted with vinylmagnesium bromide to yield 2-[1-(4-pyridyl)ethyl]-6 methoxy-1-vinyl-1-indanol. However, on dehydration this compound rearranges to 2-[1-(4-pyridyl)ethyl]-3-ethylidene-5-methoxyindene rather than the required isomer 3-ethylidine-2-[1-(4-pyridyl)ethyl]-5-methoxyindane needed fro pericyclic ring-closure to the pyrido[4,3- ]fluorene system. Reaction of -2-[1-methyl-1-(4-pyridyl)methylene]-6-methoxyindanone with ethylene triphenylphosphorane similarly gives 6-methoxy-spiro-2-[1-(2,3-dimethyl-3-(4-pyridyl)-cyclopropyl) indanone rather than the desired indane.     

Five-membered 2,3-dioxo heterocycles: LXXX. Recyclization of 1H-pyrrole-2,3-diones into pyrazolo[1,5-a]pyrimidines by the action of pyrazolamine. Crystalline and molecular structure of substituted pyrazolo[1,5-a]pyrimidine

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 3-methyl-4-phenyl-1H-pyrazol-5-amine to give methyl 7-arylcarbamoyl-6-aroyl-2-methyl-3-phenylpyrazolo[1,5-a]-pyrimidine-5-carboxylates. The molecular and crystalline structures of methyl 6-benzoyl-7-(4-chlorophenylcarbamoyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidine-5-carboxylate were studied by X-ray analysis.     

Reactions of 4,5-diamino-3-methyl-1-phenylpyrazole with aromatic haloketones

Reaction of 4,5-diamino-3-methyl-1-phenylpyrazole with -bromoacetophenones yields pyrazolo[4,5-b]pyrazines. A side product is 1-phenyl-3-methyl-5-imino-4-[(1-phenyl-3-methyl-4-aminopyrazol-5-yl)imino]-2-pyrazoline obtained by dimerization of the starting diaminopyrazole with loss of ammonia and a molecule of hydrogen.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–790, June, 1988.     

Syntheses Based on 4-Chloro-1-[3,5-di(trifluoromethyl)phenyl]-, 4-Chloro-1-(2,4-difluorophenyl)-5-formyl-3-methyl-6,7-dihydroindazoles,and 4-Chloro-5-formyl-3-methyl-1-(2-pyridyl)-6,7-dihydroindazoles

Vilsmeier formylation of 1-[3,5-di(trifluoromethyl)phenyl]- and 1-(2,4-difluorophenyl)-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles gave the corresponding 1-aryl-4-chloro-5-formyl-3-methyl-6,7-dihydroindazoles. Reaction of the latter with amidines, o-phenylenediamine, hydrazine, or hydroxylamine gave a series of 1-aryl-3-methyl-6,6-dihydroindazoles annelated at positions 4 and 5. The reaction of 4-chloro-5-formyl-3-methyl-1-(2-pyridyl)-6,7-dihydroindazole with substituted anilines gave 5-arylaminomethylene-4-oxo- or 5-arylaminomethylene-4-arylimino-3-methyl-1-(2-pyridyl)-4,5,6,7-tetrahydroindazoles depending on the molar ratio of reagents and the nucleophilicity of the amines.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 740–750, May, 2005.