Synthesis of isoquinolines and heterocycle-fused pyridines via three-component cascade reaction of aryl ketones, hydroxylamine, and alkynes

An efficient one-pot synthesis of isoquinolines and heterocycle-fused pyridines by three-component reaction of aryl ketones, hydroxylamine, and alkynes is developed. The reaction involves condensation of aryl ketones and hydroxylamine, rhodium(III)-catalyzed C-H bond activation of the in situ generated aryl ketone oximes, and cyclization with internal alkynes. This protocol enables rapid assembly of multisubstituted isoquinolines as well as γ-carbolines, furo[2,3-c]pyridines, thieno[2,3-c]pyridines, and benzofuro[2,3-c]pyridines from readily available substrates.     

Synthesis of 3-amino derivatives of benzo[b]furo[2,3-c]pyridines

The reaction of 1,7-dimethyl-3(2H)-benzo[b]furo[2,3-c]pyridone with phosphoric acid amides gave 1,7-dimethyl-3-dimethylamino (morpholino)benzo[b]furo[2,3-c]pyridines. A method for the synthesis of 3-amino derivatives of 4-nitrobenzo[b]furo[2,3-c]pyridines, which consists in heating 1,7-dimethyl-4-nitro-3(2H)-benzo[b]furo[2,3-c]pyridone with hexamethyldisilazane and secondary or primary amines in pyridine, was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1552–1555, November, 1991.     

Electrophilic cyclization of o-acetoxy- and o-benzyloxyalkynylpyridines: an easy entry into 2,3-disubstituted furopyridines

[reaction: see text] 2,3-Disubstituted furo[3,2-b]pyridines, 2,3-disubstituted furo[2,3-b]pyridines, and 2,3-disubstituted furo[2,3-c]pyridines are readily prepared under mild conditions via the palladium-catalyzed cross-coupling of 1-alkynes with o-iodoacetoxy- or o-iodobenzyloxypyridines, followed by electrophilic cyclization by I(2) or by PdCl(2) under a balloon of carbon monoxide.     

Nouvelles voies d'accès à des aryl-4 thiéno[2,3-c]pyridines et à des aryl-7 thiéno[3,2-c]pyridines

4-Arylthieno[2,3-c]pyridines and 7-arylthieno[3,2-c]pyridines have been prepared by heating in polyphosphoric acid 2-(2-thenylamino>l-arylethanols or propanols and 2- 3-thenylamino>l-arylethanols or propanols, respectively.) Under the Beckmann rearrangement conditions, oximes of 4-aryl-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one lead to 4-aryl-4,5- dihydro-6H-thieno[2,3-c]pyridin-7-one.     

The Synthesis of Some New Fused and Substituted Chromenes

Some new chromeno[2,3-b]pyrimidines, chromeno[3,2-c]pyridines, chromeno[2,3-b]pyridines and 3-chromenyl-1,3-thiazines were synthesized via the synthetic studies of the reaction of 2-imino-2H-chromen-3-thiocarboxamide with some aromatic aldehydes, active nitriles, and their ylidene derivatives.     

Interaction of benzothieno[2,3-c]pyrylium salts with hydrazine. Derivatives of 5H-[2,3]benzothieno[2,3-e]diazepines

A study has been made of the reaction of 1,3-disubstituted bezothieno[2,3-c]pyrylium salts with hydrazine. It has been shown that 1,3-dialkyl-substituted benzothieno[2,3-c]pyrylium salts interact with hydrazine to give N-amino-1,3-dialkylbenzothieno[2,3-c]pyridines. The presence of a pyrylium ring on one of the positions of the phenyl group leads to a mixture of N-amino derivatives and 5H-[2,3]benzothieno[2,3-e]diazepines. In contrast, 1,3-diphenylbenzothieno[2,3-c]pyrylium perchlorate gives exclusively 5H-[2,3]benzothieno[2,3-e]diazepine.L. M. Litvinenko Institute of Physical Organic Chemistry and Coal Tar Chemistry, National Academy of Sciences of Ukraine, Donetsk 340114. Translate from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp 1137–1140, August, 1998.     

Synthesis and molecular structure of 4-nitro-9-phenyl-1H-and 9-hydroxy-3-oxo-9-phenyl-2,3-dihydro-9H-indeno-[2,1- c ]pyridines and 3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1- c ]isoxazolo[5,4- d ]pyridine

The 4-nitro derivatives and an oxidation by-product, 9-hydroxy-2-methyl-3-oxo-9-phenyl-2,3-dihydro-9H-indeno[2,1-c]pyridine were obtained by the nitration of N-alkyl-9-phenyl-2,3-dihydro-1H-indeno-[2,1-c]pyridines with sodium nitrite in acetic acid. Their molecular structures were studied by X-ray structural analysis. The product of [2+3] cycloaddition, 5-methyl-3,7-diphenyl-3a, 4,5,6-tetrahydroindeno[2,1-c]isoxazolo[5,4-d]pyridine, was obtained by the interaction of 2-chloro-1-hydroxy-2-phenylazomethine with 2-methyl-9-phenyl-2,3-dihydro-1H-indeno[2,1-c]pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1390–1399, September, 2007.     

Novel Synthetic Route Toward Benzofuran-pyridine–Based Spirans

A novel domino reaction of tetrahydrobenzofuro[3,2-c] or [2,3-c]pyridines with dimethylacetylene dicarboxylate (DMAD) or methyl propiolate (MP) resulted in the formation of spirobenzofuranpyridines in moderate yields. The spirobenzofuran derivatives reported may be considered analogs of the antifungal drug griseofulvin.     

Synthesis of novel condensed pyridines and pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

Methods have been developed for the synthesis of novel derivatives of pyrano[3,4-c]pyridines, 2,7-naphthyridines, and condensed pyrido[2,3-d]pyrimidines by condensation of thiopyranthiones.     

Synthesis and reactions of benzo[b]thieno[2,3-c]pyrylium pairs

Benzo[b]thieno[2,3-c]pyrylium perchlorates were obtained in high yields in the acylation of benzo[b]thien-3-ylacetone with aliphatic acid anhydrides in the presence of 70% perchloric acid. Treatment of the products with ammonia converts them to benzo[b]thieno[2,3-c]pyridines (in yields higher than 90%), whereas hydroxy and dialkylamino derivatives of dibenzothiophene were obtained in up to 50% yields by treatment of the products with alkalis or secondary amines, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1351–1354, October, 1981.     

Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols

The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.     

Synthesis and mode of action of (125)I- and (3)H-labeled thieno[2,3-c]pyridine antagonists of cell adhesion molecule expression

A series of thieno[2,3-c]pyridine antagonists of cell adhesion molecule (CAM) expression, such as A-205804 (1) and A-249377 (2), selectively suppressed the induced expression of E-selectin and ICAM-1 over VCAM-1. In an effort to explore the biological mechanism of action of these inhibitors, we synthesized (125)I- and (3)H-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazonium tetrafluoroborate salt efficiently trapped Na(125)I on very small scale (7.5 microg of Na(125)I), providing the corresponding (125)I-labeled thieno[2,3-c]pyridine in modest yield. Preliminary mechanistic investigations using these radiolabeled compounds revealed that, upon incubation with human umbilical vein endothelial cells (HUVECs), these inhibitors of CAM expression translocated to the cell nucleus and were noncovalently associated with macromolecules of molecular weight greater than 650 kDa.     

6-[(Dimethylamino)methylene]amino-1,3-dimethyluracil: A versatile aza-diene substrate for cycloaddition and michael-type reactions

6-[(Dimethylamino)methylene]amino-1,3-dimethyluracil 1 undergoes formal [4+2] cycloaddition reactions with electron deficient olefins to give pyrido[2,3-d]pyrimidines. With DMAD or azodicarboxylates Michael addition occurs leading to pyrrolo[3,4-c]pyridines (X-ray analysis) and theophylline derivatives.     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

Nucleophilic displacement of aromatic fluorine,Part III,indoloquinolines and benzofuranoquinolines

Variously substituted indolo[2,3-c]quinolines, benzofurano[2,3-c]quinolines and their positional isomers indolo[3,2-c]quinolines and benzofurano[3,2-c]quinolines respectively, were prepared from both indole and quinoline derivatives by intramolecular nucleophilic displacement of aromatic fluorine. The formation of an indolo[2,3-d]benzazepine was also observed.     

Aza and deaza analogs of purine nucleosides (review)

Methods for the preparation of aza and deaza analogs of purine nucleosides, viz., nucleosides of imidazo[4,5-d]-v-triazines, imidazo[4,5-b]pyridines, and imidazo[4,5-c]pyridines, and their properties are described. References to the synthesis of nucleosides of imidazo[4,5-d]pyridazines, imidazo[4,5-c]pyridazines, and imidazo[4,5-b]pyrazines are also given.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 147–161, February, 1981.     

Etude cinétique comparée de la substitution nucléophile de quelques chloro-2 pyridines condensées

A comparatie kinetic study of nucleophilic substitution of some condensted 2-chloropyridines by piperidine was carried out and an “autocatalytic effect” was observed in the case of 1-methyl-4-chloro-5-azaindole. The rate constants of such substitutions were determined for 1-methyl-4-chloro-5-azaindole, 4-chlorofuro[3,2-c]pyridine, 1-phenyl- and 1-benzy;(1H)pyrazolo[4,3-c]pyridines, 4-chloro-6,7-dimethylpyrrolo[2,3-d]pyrimidine, and a classification of reactivity of these compounds, as compared to 2-chloropyridine, was established.     

Interaction of 4,5,7-Trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines with Acetic and Trifluoroacetic Anhydrides

The reactions of NH- and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo-[3,2-c]pyridines and their 2-substituted derivatives with acetic and trifluoroacetic anhydrides have been studied. Trifluoroacetylation of tetrahydropyrrolo-[3,2-c]pyridines occurs at the α-position of the pyrrole ring, whereas cleavage of the tetrahydropyridine ring with formation of 3-vinylpyrroles occurs with acetic anhydride. 2-Acetyl-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine was synthesized by the Vilsmeier-Haack reaction.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, 751–760. May, 2005.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

Polysubstituted 2,3-dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano[2,3-b]pyridines via microwave-activated inverse electron demand Diels-Alder reactions

Polysubstituted 2,3-dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano[2,3-b]pyridines have been synthesized from 1,2,4-triazines using the inverse electron Diels-Alder reaction. For this purpose, 3-methylsulfanyl-1,2,4-triazines were reacted with several nucleophiles allowing the formation of appropriately substituted alkynes to undergo the intramolecular inverse electron demand Diels-Alder reaction. Sealed-tube microwave activation of the cycloaddition reaction has proved to be very efficient and allowed shorter reaction times. This strategy enabled an efficient synthesis of 3-hydroxy-2,3-dihydrofuro[2,3-b]pyridines and 4-hydroxy-3,4-dihydro-2H-pyrano[2,3-b]pyridines with several points of diversity on the bicyclic scaffold.