An effective method for the preparation of mono N-alkyl derivatives of 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline)

The condensation of 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) with alkyl, aralkyl and aryl aldehydes, but not ketones, in ethanol or chloroform provides useful cyclic aminal [8-substituted 5,6,10,11,15b,15c-hexahydro-2,3,13,14-tetramethoxy-8H-imidazo[5,1-a:4,3-a′]diisoquinoline] intermediates that when subsequently treated with sodium cyanoborohydride in ethanol, followed by the addition of 2 M hydrochloric acid, gave monosubstituted N-alkyl 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) derivatives in very high yields. The rates of the initial condensation with four different aldehydes were measured, and the entire sequence was successfully applied in one example to a ‘one-pot’ process; this signals a versatile route to differentially N-substituted 1,1′-bis(1,2,3,4-tetrahydroisoquinoline) derivatives.     

Synthesis of some fused quinoline derivatives

Summary Preparations of the novel fused dimethoxyquinoline derivatives of furo[2,3-b]quinoline (5),s-triazolo[4,3-a]quinoline (8) and tetrazolo[1,5-a]quinoline (10) from 6,7-dimethoxy-3-car-boxyquinoline-1-oxide (1) are reported.

---

Synthese kondensierter Chinolinderivate

Zusammenfassung Die Synthese der neuen kondensierten Dimethoxy-Chinolinderivate Furo[2,3-b]chinolin (5),s-Triazolo[4,3-a]chinolin (8) und Tetrazolo[1,5-a]chinolin (10) aus 6,7-Dimethoxy-3-carboxychinolin-1-oxid (1) wird beschrieben.

     

Reactions of 6,7-dimethoxy- 3,4-dihydroisoquinoline with <Emphasis Type="Italic">o</Emphasis>-quinone methides

Products of heterocyclization, 9,10-dimethoxy-12,13-dihydro-7aH,15H-naphtho[1',2':5,6][1,3]oxazino-[2,3-a]isoquinolines, were isolated on condensing 6,7-dimethoxy-3,4-dihydroisoquinoline with 1-dimethylaminomethyl-2-naphthols. In the case of o-hydroxybenzyl alcohols products of a Michael aza reaction, 2-[(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)methyl]phenols were obtained.     

New heterocyclic sym-triazolopyrimidinium systems — Quinoline,pyridazine, and phthalazine derivatives

Pyrimido[1′,2′:1,5]-sym-triazolo[4,3-b]pyridazinium, pyrimido[1′,2′:1,5]-sym-triazolo-[4,3-b]phthalazinium, and pyrimido[1′,2′:1,5]-sym-triazolo[4,3-a]quinoliniumsalt derivatives were obtained by condensation of 3-amino-sym-triazolo[4,3-b]pyridazinium, 3-amino-sym-triazolo[3,4-a]phthalazinium, and 1-amino-sym-triazolo[4,3-a]quinolinium salts with β-diketories and 1,1,3,3-tetraethoxypropane. The structures of the reaction products were confirmed by the P MR spectra.     

Complete assignments 1H and 13C NMR spectral data of four anabaseine derivatives

The anabaseine derivatives 6-methoxy-7-hydroxy-1-(pyridin-3-yl)-3,4-dihydroisoquinoline, 6,7-dimethoxy-1-(pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline and 6,7-dimethoxy-1-(piperidin-3-yl)-1,2,3,4-tetrahydroisoquino- line were prepared either by demethylation with HBr or by reduction with different reagents, NaBH4 and H2/PtO2 from 6,7-dimethoxy-1-(pyridin-3-yl)-3,4-dihydroisoquinoline, as starting material. The structures have been fully assigned by the combination of one- and two-dimensional experiments.     

Synthesis and conversions of 2-aryl derivatives of s-triazolo[4,3-a]pyrimidine

The reaction of arylhydrazines and 1-ethoxycarbonyl-2-methylthio-1,4,5,6-tetrahydropyrimidines forms 2-aryl-3-oxo-2,3,5,6,7,8-hexahydro-s-triazolo[4,3-a]pyrimidines. The reaction of 2-phenyl substituted triazolo[4,3-a]pyrimidine with various acylating agents to give 8-acyl derivatives and the effect thereon of hydrogen chloride were studied. The amine-imine tautomerism of these compounds was studied by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1350–1353, October, 1986.     

Mannich-type reactions of an isobasic isoquinoline

Base catalyzed reaction of 1-cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahyroisoquinoline (I) with 2 moles of formaldehyde gave rise to the 1,3-oxazino[4,3-a ]isoquinoline ring system (III). Reaction of I with a primary amine and 2 moles of formaldehyde gave pyrimido[ 6,1-a ]-isoquinoline (VI).     

Isoquinoline derivatives

6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-4-spirocyclopentane was obtained by condensation of 3,4-dimethoxyphenyl-1-(aminomethyl)cyclopentane with formalin. The corresponding amides, which were reduced to tertiary amines, were synthesized by reaction of the latter with the acid chlorides of substituted benzoic and phenylacetic acids. Substituted dibenzo[a,-g]quinolizines, isoindolo[1,2-a]isoquinolines, and 1-(3,4-dimethoxyphenyl)-1-[(6,7-dimethoxy-1, 2,3,4-tetrahydro-2-isoquinolinyl)methyl]cyclopentane were synthesized, respectively, by condensation of 1-aryl (or aralkyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-4-spirocyclopentanes and their open analog -1-(3,4-dimethoxyphenyl)-1-(3,4-dimethoxyphenylethylaminomethyl)cyclopentane — with formalin.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 679–682, May, 1973.     

4-Hydroxy-2-quinolones. 180*. Synthesis,chemical reactions,and analgesic activity of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

A targeted synthesis was carried out of a series of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid alkylamides which show interest for biological study as potential analgesics. It was found that, in the presence of one equivalent of bromine, the compounds indicated undergo halocyclization to the corresponding 2-bromomethyl-7,8-dimethoxy-5-oxo-1,2-dihydro-5H-oxa-zolo[3,2-a]quinoline-4-carboxylic acid alkylamides. However, with an excess of bromine the reaction occurs somewhat differently and concludes with the formation of complexes of bromine with 4-alkyl-carbamoyl-2-bromomethyl-5-hydroxy-7,8-dimethoxy-1,2-dihydrooxazolo[3,2-a]quinolinium ditri- bromides. According to the results of pharmacological screening there are found compounds within the substances discovered with high analgesic activity.     

Efficient and general synthesis of oxazino[4,3-a]indoles by cascade addition-cyclization reactions of (1H-indol-2-yl)methanols and vinyl sulfonium salts

An efficient and general approach to oxazino[4,3-a]indole architectures is described. The addition-cyclization cascade of (1H-indol-2-yl)methanols with vinyl sulfonium salts affords oxazino[4,3-a]indole derivatives in high yields.     

Isoquinoline derivatives VI. Synthesis and pharmacological properties of 4,6,7-substituted 1(2)-arylalkyl-1,2,3,4-tetrahydroisoquinolines and their analogs

The condensation of 6,7-dimethoxy-1,2.3.4-tetrahydroisoquinoline (II) with diphenylacetyl and diphenylpropionyl chlorides gave the corresponding amides (III). Reduction of III with lithium aluminum hydride converted them to tertiary amines IV, which were characterized as their hydrochlorides. The condensation of equimolecular amounts of amines I with the acid chlorides of substituted phenylacetic and diphenylpropionic acids gave amides V. The reduction of amides V with lithium aluminum hydride gave secondary amines VI. The corresponding tetrahydroisoquinolines (VII) were obtained by the cyclization of amides V and subsequent reduction with lithium aluminum hydride, The condensation of 1-diphenylethyl-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with formalin gave VIII. The IR spectra of the synthesized compounds were examined. The effect of these compounds on the arterial blood pressure and the coronary blood flow was studied.See [1] for communication V.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1683–1687, December, 1971.     

Synthesis of Novel Benzotriazoloazepine Derivatives

Eight new benzotriazoloazepine derivatives have been synthesized starting from 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐2‐benzo[c]azepin‐1‐one. The compounds 2a–c have been synthesized by the reaction of 7‐methoxy‐2,3,4,5‐tetrahydro‐1H‐2‐benzo[c]azepin‐1‐thione with various hydrazides. Reaction of 5 with hydrazine hydrate, followed by treatment of the resultant hydrazone with formic acid, gave corresponding 9‐alkoxy‐6,7‐dihydro‐5H‐benzo[c][1,2,4]triazolo[4,3‐a]azepine(6 a , b ). Cyclization of 5 with methyl carbazate gave 9‐alkoxy‐6,7‐dihydro‐2H‐benzo[c][1,2,4]triazolo[4,3‐a]azepin‐3(5H)‐one (7 a–c ). The structures of the compounds were confirmed by their elemental analysis and spectral data. Their anticonvulsant activities have been initially screened.     

Enamines of the 1,2,3,4-tetrahydroiso-quinoline series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalyl chloride

It has been shown that the Chichibabin reaction of enamines of the 1,2,3,4-tetrahydroisoquinoline series and 1,2,3,4-tetrahydrobenzo[f]isoquinoline series with p-bromophenacyl bromide leads to pyrrolo[2,1-a]isoquinoline derivatives. The same heterocyclic system is obtained on interaction of 1-alkyl-3,4-dihydroisoquinolines or their benzo[f]-analogs with oxalyl chloride. The obtained dioxopyrrolines form derivatives of benzo[g]quinoxalino[2,3-b]indolizine on condensation with o-phenylenediamine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1068–1074, July, 2007.     

Heterocyclization of 1,1-dicyano-2-(trifluoromethyl)ethylenes with 1,3,3-trimethyl-3,4-dihydroisoquinoline and its derivatives

1,3,3-Trimethyl-3,4-dihydroisoquinolines react with 1,1-dicyano-2,2-bis(trifluoromethyl)ethylene to give 4-amino-6,6-dimethyl-2,2-bis(trifluoromethyl)-3-cyano-6,7-dihydro-2H-benzo[a]quinolizines. The reaction of 3,3-dimethyl-1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline and the methyl ester of 3,3-dicyano-2-(trifluoromethyl)acrylic acid leads to 5,5-dimethyl-3-oxo-2-(trifluoromethyl)-2-(dicyanomethyl)-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1888–1892, August, 1992.     

The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.     

Ten π -electron nitrogen heterocyclic compounds:X the syntheses and structure determinations of some 1,2,4-triazolopyrimidines

It has been shown that the reaction of 2-hydrazinopyrimidines with ethyl orthoesters yields 1,2,4 -triazolo[4,3 -a]pyrimidines as well as 1,2,4-triazolo[1,5-a]pyrimidines. The structures of the parent compounds and of some methyl derivatives have been established by NMR spectroscopy.     

On Triazoles. XIII. The reaction of 5-benzalimino-1,2,4-triazoles with substituted acetyl chlorides

The reaction of Schiff bases prepared from 1- and 2-substituted-5-amino-1,2,4-triazoles with phenoxyacetyl chlorides in the presence of triethylamine and a mixture of phosphorus oxychloride and dichloroacetic acid in dimethylformamide to yield β-lactam 4 , a dihydro-1,2,4-triazolo[4,3-a]pyrimidine-5(1H)-one 5, a 1,2,4-triazolo[1,5-a]pyrimidin-5(3H)-one 9 and the corresponding 1,2,4-triazolo[4,3-a]pyrimidine-5(1H)-one 10 derivatives was studied.     

1,2,4-Triazoles—XXXIV: Photodimerization of some 1,2,4-triazo[4,3--]quinoline and 1,2,4-triazolo[3,4-a]isoquinoline derivatives

Irradiation of 1,2,4-triazolo[4,3-a]quinoline and several Me derivatives at 300 nm afforded the cisoid-fused, head-to-tail cyclobutane dimers 7bα,7cα,14bα,14cα - tetrahydro - 1,2,3a,8,9,10a - hexaazadibenzo [c,i]dicyclopenta[a,g]biphenylenes. However, 1,2,4 - triazolo[3,4-a]isoquinolines gave analogous cisoid-fused, head-to-head dimers except for the 5-Me derivative where the head-to-tail dimer was obtained.Codimerization occurred when 1 - methyl - 1,2,4 - triazolo[4,3-a]quinoline and 5 - methyl - 1,2,4 -triazolo[3,4-a]isoquinoline were irradiated at 300 nm, affording a cisoid-fused head-to-tail cyclobutane co-dimer as the single photoproduct. However, irradiation of their 5-Me substituted derivatives at 300 nm afforded the cisoid-fused, head-to-head, cyclobutane codimer and also a minor amount of the dimer derived from 5 - methyl -1,2,4- triazolo[4,3-a] quinoline. Irradiation of equimolar quantities of 2(1H)-quinolinone and 5 - methyl - 1,2,4 -triazolo [4,3-a]quinoline at 300 nm gave the known 2(1H)-quinolinone dimer and a minor amount of a cisoid-fused co-dimer of undetermined configuration.     

sym-Triazolo[4,3-a][1,3]diazacycloalkanes. 4. Synthesis and transformations of 2-aminothiocarbonyl-sym-triazolo[4,3-a]pyrimidine

In the reaction of 1-ethoxycarbonyl-2-methylthio-1,4,5,6-tetrahydropyrimidine with thiosemicarbazide, 2-aminothiocarbonyl-3-oxo-2,3,5,6,7,8-hexahydro-sym-triazolo[4,3-a]pyrimidine is formed, which as a result of the successive action of methyl iodide, K₂CO₃ solution, and cyclic amines, converts into 2,3,5,6,7,8-hexahydro-8-oxo-sym-triazolo[4,3-a]pyrimidine.For Communication 3, see [1]Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1540–1542, November, 1987.     

Saturated heterocycles, 162 [1]. synthesis and steric structures of 3,4-disubstituted 1,6,7,11b-tetrahydropyrimido[6,1-a]isoquinolin-2-ones

The reaction of 1-(hydrazidomethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 3 with aromatic aldehydes yield hydrazones 4a,b or pyrimido[6,1-a]isoquinolines 5a-c depending upon the proportions of the reagents. With ketones, 3 gives only hydrazones 4a-d and 7 , which can be transformed to pyrimidoisoquinolines 10a-e and 11 with aldehydes. The ring closures are stereospecific; the relative configurations were determined by DNOE measurements.