Povarov reactions involving 3-aminocoumarins: synthesis of 1,2,3,4-tetrahydropyrido[2,3-c]coumarins and pyrido[2,3-c]coumarins

Condensation of 3-aminocoumarin (5) with 4-nitrobenzaldehyde (8) afforded a 2-azadiene (9), which reacted with various electron-rich alkenes (10 examples) in the presence of Yb(OTf)3 to afford 1,2,3,4-tetrahydropyrido[2,3-c]coumarins. Yields were generally good, but the diastereomeric ratios were highly variable. The products arose through a formal [4 + 2] cycloaddition (inverse electron demand Diels-Alder reaction) followed by tautomerization. As such, these are examples of the Povarov reaction. A range of 1,2,3,4-tetrahydropyrido[2,3-c]coumarins was then synthesized using a three-component version of this reaction, which involves in situ formation of the 2-azadiene component. Some of these products were converted into the corresponding pyrido[2,3-c]coumarins upon treatment with various oxidants, the most effective of which proved to be nitrous gases.     

Synthesis of 4,7-diaminopyridazino[4,5-c]furoxan

4,7-Diaminopyridazino[4,5-c]furoxan was synthesized by intramolecular cyclization of 3-cyanofuroxan-4-carbamidrazone obtained from 3,4-dicyanofuroxan and hydrazine.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1559–1560, August, 1995.     

Synthesis of pyrido[3,2-c]pyridazines

The synthesis of some 3-methylpyrido[3,2-c]pyridazines substituted at positions 6 and 6,7 is described. The first step of the preparation of an aza analog of ellipticine is studied.     

A novel crystalline tetrazolo-azido isomer pair: Pyrido[ 2,3-e] tetrazolo[5,1-c]-as-triazine and 3-azidopyrido[2,3-e]-as-triazine; the synthesis of tetrazolo[5,1-c] benzo-as-triazine and pyrido[2,3-e]-s-triazolo[3,4-c] -as-triazine

The deoxygenated derivative of 3-azidobenzo-as-triazine 1-oxide (II) exists in solution predominantly as 3-azidobenzo-as-triazine form (IVa) but in the crystalline state as tetrazolo[5,]-c]-benzo-as-triazine (IVb), a new fused heteroaromatie ring system. With the pyrido[2,3-e]-as-triazine derivatives, however, both 3-azidopyrido[2,3-e]-as-triazine (X) and pyrido[2,3-e] tetra-zolo[5,1-e]-as-triazine (XI) can be isolated in crystalline form, and these are interconvertible. Another new ring system, the pyrido[2,3-e] triazolo [3,4-c]-as-triazine (XVII) and its derivatives has also been synthesized.     

1,4-Cycloaddition reactions. III. Synthesis of furo[3,2-c]pyrido[2,3-g]quinolines,Furo[2,3-a] [4,7]phenanthrolines,Furo[3,2-c]pyrrolo[2,3-g]quinolines,Furo[3,2-c]pyrrolo[3,2-g]quinolines,and Furo[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinolines from 2,3-dihydro-5-methylfuran and schiff bases

The 1,4-cycloaddition of 2,3-dihydro-5-methylfuran (II) to 1-acetyl-1,2,3,4-te trahydro-6-[(p-hydroxybenzylidene)amino]quinoline (VIII) in the presence of boron trifluoride gave two pairs of epimers, namely dl-10-acetyl-2,3,3a,4,5,7,8,9,10,11b-decahydro-4-(p-hydroxyphenyl)-11b-methylfuro[3,2-c]pyrido[2,3-g]quinoline (IXa and b) and dl-8-acetyl-2,3,3a,4,5,8,9,10,11,-11c-decahydro-4-(p-hydroxyphenyl)-11c-methylfuro[2,3-a][4,7]phenanthroline (Xa and b). dl-9-Acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c] pyrrolo-[2,3-g]quinoline (XIIIa) was the predominant product isolated from the reaction of II with 1-acetyl-5-[p-(hydroxybenzylidene)amino]indoline (XII). When 1-acetyl-6-[(p-hydroxybenzylidene)amino]indoline (XVI) was treated with 2,3-dihydro-5-methylfuran (II), two epimers of dl-7-acetyl-3,3a,4,5,7,8,9,10b-octahydro-4-(p-hydroxyphenyl)-10b-methyl-2H-furo[3,2-c]pyrrolo[3,2-g]quinoline (XVIIa and b) were obtained. dl-2,3,3a,4,5,6b,8,9,9a,10,11,12b-Dodecahydro-4,10-bis(p-methoxyphenyl)-6b,12b-dimethylfuro[3,2-c]furo[2′,3′:4,5]pyrido[2,3-g]quinoline (XX) was formed when 2,3-dihydro-5-methylfuran was allowed to react with N,N'-bis(p-methoxybenzylidene)-p-phenylcnediamine (XIX). Structure assignments were made from NMR spectra. None of the compounds exhibited appreciable biological activity.     

A new synthesis of 2,3-dihydrofuro[2,3-b], [2,3-c] and [3,2-c]quinolines

A new synthesis of three isomeric dihydrofuroquinolines is described. This route via ortholithiation of O-quinolyl carbamates is considerably more effective than that which proceeds via lithiation of alkoxyquinolines.     

Synthesis of 1H-pyrazino[1,2-a]pyrido[2,3-e]pyrazine and 2H-Pyrano[2,3-b]pyrido[2,3-e]pyrazine Derivatives

With a continuing interest on heteropolycyclic structures which may show biological activities, we synthesized new tricyclic derivatives in which the pyridopyrazine skeleton is fused with pyrazine 7 and 8, B , n = 1. However, the initial design of obtaining also the cyclohomologous structure B (n = 2) produced instead a pyranopyridopyrazine derivative 11 . Thus during the attempt to prepare a pyridodiazepine intermediate, beside a very small amount of the desired product 10 , the pyridopyrazine 9 was obtained. The latter compound reacted with chloroacetyl chloride/chloroketene to give 4-carbethoxy-10-(chloroacetyl)-5,10-dihydro-5-methyl-2H-pyrano[2,3-b]pyrido[2,3-e]pyrazin-2-one ( 11 ). In studying the behavior of this derivative, compounds 12–14 were obtained. Compounds 4b,c, 5a,b, 7, 8, 9 and 14 have been submitted to preliminary pharmacological screening as CNS depressant agents.     

1,2,4-Triazino[4,3-c]- and [2,3-c]quinazolines

This paper describes the reactions of 2-o-aminophenyl-1,4,5,6-tetrahydro-1-methyl-1,2,4-triazine with a variety of reagents to give substituted 1,2,4-triazino[4,3-c]quinazolines or 1,2,4-triazino[2,3-c]quinazolines. Certain representative compounds of these two new heterocyclic systems were characterized by the tlc, ir, nmr, mass spectra, and identified by unequivacol synthesis.     

The synthesis of pyrimido[4,5-c] pyridazines and pyrido[2,3-d]pyrimidines related to toxoflavin and fervenulin

4-Deazatoxoflavin (1,6-dimethyl-1,5,6,7-tetrahydropyrimido[4,5-c]-5,7-pyridazinedione) ( 7 ) and several other 4-deazatoxoflavin and 4-deazafervenulin analogs have been prepared with the required intermediates. 3,5,7-Trimethyl-1,2,3,4-tetrahydropyrido[2,3-d]-2,4-pyrimidinedione ( 19 ) and 8-phenyl-3,5,7-trimethyl-2,3,4,8-tetrahydropyrido[2,3-d]-2,4-pyrimidinedione ( 20 ) were also prepared.     

A New synthesis of 4,5,6,7-tetrahydrofuro[2,3-c]pyridines and furo[2,3-c]pyrrolidines

New syntheses of 4,5,6,7-tetrahydrofuro[2,3-c]pyridines and furo[2,3-c]pyrrolidine derivatives, starting from furan-3-carboxaldehyde, are reported.     

Synthesis of new pyrido[3,4-c]carbazole derivatives

Previously unknown 2-[6-hydroxy-9-(4-methoxyphenyl)-1,2,3,9-tetrahydro-4H-carbazol-4-ylidene]malononitrile was synthesized by the Nenitzescu reaction and was used for the construction of new tetracyclic compounds, viz., pyrido[3,4-c]carbazoles. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1600–1604, September, 2006.     

The synthesis of [1]benzothieno[2,3-c]quinolines, [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline,and [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline

Photocyclization of 3-chloro-N-phenylbenzo[b]thiophene-2-carboxamide 10 afforded [1]benzothieno[2,3-c]-quinolin-6(5H)-one 11 which was chlorinated to 6-chloro[1]benzothieno[2,3-c]quinoline 12 followed by dechlorination to give [1]benzothieno[2,3-c]quinoline 5 . A series of 6-substituted alkoxy and thioalkoxy[1]benzothieno[2,3-c]quinoline derivatives were prepared along with the N-methyl quaternary salt 13 of 5 . 6-Chloro[1]-benzothieno[2,3-c]quinoline 12 was converted into 6-hydrazino[1]benzothieno[2,3-c]quinoline 23 which upon treatment with formic acid yielded [1]benzothieno[2,3-c][1,2,4]triazolo[4,3-a]quinoline 6 . Treatment of 23 with nitrous acid resulted in [1]benzothieno[2,3-c]tetrazolo[1,5-a]quinoline 7 . Compounds 6 and 7 are novel heterocyclic ring systems.     

Condensed pyridine bases synthesis of some benzo[b]furo[2,3-c]-, benzo[b]- thieno[2,3-c]-, and benzo[b]selenopheno[2,3-c]-quinolines

Summary Condensation of benzo[b]furan-3(2H-one, benzo[b]thiophen-3(2H)-one and benzo[b]selenophen-3(2H)-one with dimedone gives 2-(3-heteryl)dimedones. Acylation of the latter leads to the corresponding tetracyclic pyrylium salts, from which condensed quinolines are obtained. Some condensed quinoline derivatives are obtained by reaction of 1-oxo-1,2,3,4-tetrahydroheterene[2,3-c]quinolines with sodium borohydride, hydrazine, and hydroxylamine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 321–326, March, 1994.     

Synthesis of [1,4]dioxino[2,3-c]quinolines and [1,4]dioxepino-[2,3-c]quinolines and their 1-sulfur analogues

The synthesis of [1,4]dioxino[2,3-c]quinolines and [1,4]dioxepino[2,3-c]quinolines with restrained conformation of the piperidine ring, which represent 1,2,3,4-tetrahydroquinolines containing two heteroatom substituents at positions 3 and 4, is described. In addition, the application of this approach for the synthesis of 1-sulfur analogues is discussed. Both series are helpful tools for three-dimensional quantitative structure-activity relationship studies in the field of modulators of multidrug resistance.     

Pyrido[2,3-c]furoxan as a probable intermediate in the reaction of 2-nitro-3-azidopyridine with amines

Two parallel reactions, viz., cyclization of 2-nitro-3-azidopyridine to pyrido-[2,3-c]furoxan, which is aminated in the 6 position of the pyridine ring with opening of the furoxan ring, and reduction of the azido group to form 2-nitro-3-aminopyridine, occur in the reaction of 2-nitro-3-azidopyridine with amines. It was established that pyrido[2,3-c]furoxan reacts with amines in aqueous media in the 1-oxide form.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 654–657, May, 1981.     

Calculation of electronic spectra of pyrido [2,3-d]pyridazine and pyrido[3,4-d]pyridazine

The electronic spectra of pyrido[2,3-d]pyridazine and pyrido[3,4-d]pyridazine have been calculated by the P method and the RP method previously used for azines. The results are in good agreement with experimental data and with the previous conclusions.     

1,2,4-Triazino[4,3-c]- and [2,3-c]quinazolines. II

This paper describes the results of allowing a variety of reagents, such as, aldehydes, ketones, carboxylic acids, acid chlorides, ortho esters, isocyanates, S-methylisothiourea, carbon disulfide, phosgene, nitrous acid, and cyanogen bromide to react with the multifunctional compound, 3-(o-aminophenyl)-1-methyl-1,4,5,6-tetrahydro-1,2,4-triazine.     

Regioselective synthesis of pyrido[2,3-d]pyrimidines

The reaction of diethyl ethoxymethylenemalonate ( 1 ) and 6-amino-1,3-dimethyluracil ( 2 ) was determined to be regioselective. Under acidic conditions the product was the previously isolated 7-oxopyrido[2,3-d]pyrimidine ( 3 ), while in the presence of one equivalent of base followed by thermal cyclization, the isomeric 5-oxopyrido[2,3-d]pyrimidine ( 5 ) is formed.     

Novel heterocycles. 4. Synthesis of the pyrido[2,3-c]-1,2-thiazine ring system

The reaction of 2-chloronicotinonitrile with N-methylmethanesulfonamide and subsequent treatment with base furnished the novel pyrido[2,3-c]-1,2-thiazine ring system 7 . Spectrally, it was determined that the predominant tautomer in solution was the 4-amino form 7a . Acidic hydrolysis of 7 furnished the 4-oxo tautomer 8b , compound 8b was alkylated on oxygen with 1-bromopentane in the presence of sodium hydride. Reaction of 8b with isocyanates occurs at the 3 position to produce carboxanilides 10 . Spectral characteristics of these compounds are also discussed.     

The synthesis of a pyrido[2,3-c]pyridazine: A cinnoline related to 6-fluoronalidixic acid

An analog of the pyrido[2,3-c]pyridazine ring system, 1-ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxopyrido-[2,3-c]pyridazine-3-carboxylic acid ( 13 ), related to both Cinoxacin ( 1 ) and nalidixic acid ( 2 ), has been synthesized. The reductive ring closure of 2-chloro-α-diazo-6-methyl-5-nitro-β-oxo-3-pyridinepropanoic acid, ethyl ester ( 7 ), proved to be the key reaction providing entry into the ring system.