A facile synthesis of 2,3-disubstituted furo[2,3-b]pyridines

In a three-step sequence starting from readily available starting materials, 2,3-carbon disubstituted furo[2,3-b]pyridines can be accessed in good yields and purity. Furo[2,3-b]pyridines bearing ester, amide and ketone groups at the 2-position can be prepared with a variety of aryl and alkyl groups at the 3-position.     

A simple method for the preparation of selenopheno[3,2-b] and [2,3-b]thiophenes

A simple strategy for the preparation of novel selenopheno[3,2-b] and [2,3-b]thiophenes by treatment of ethynylthiophenes with selenium(I), (II), and (IV) chlorides and bromides is elaborated.     

Synthesis of 7-ethyl-4,7-dihydro-4-oxo-2-(4-pyridinyl)thieno[2,3-b]pyridine-5-carboxylic acid

7-Ethyl-4,7-dihydro-4-oxo-2-(4-pyridinyl)thieno[2,3-b]pyridine-5-carboxylic acid ( 4 ), an analog of nalidixic acid, was synthesized in seven steps starting from commercially available 4-methylpyridine. Bacterial susceptibility to compound 4 was tested and the title compound was found to exhibit only weak antibacterial activity against a variety of pathogens including S. Aureus, E. Coli and P. Aeruginosa.     

Synthesis of benzothiopyrano[2,3-b]indol-11-one and benzopyrano[2,3-b]indol-11-one

The fused heterocycles benzothiopyrano[2,3-b]indol-11-one and benzopyrano[2,3-b]indol-11-one, have been prepared from methyl 3-indole carboxylate in two steps.     

Fused pyrazino[2,3-b]indolizine and indolizino[2,3-b]quinoxaline derivatives; synthesis, structures, and properties

The synthesis of six new compounds incorporating either a pyrazino[2,3-b]indolizine or indolizino[2,3-b]quinoxaline core are reported in good yield (58-87%). The intermediates for the key cyclization reaction for one set of compounds (5a-c), with a sterically demanding 3,5-dimethylpyrazole group in the 5-position of the core, were found to be mono-substituted. These intermediates could be isolated and cyclized by heating under acid-catalyzed conditions. To further demonstrate the versatility of the chemistry, compounds 6a-c were synthesized in 58-68% yields. Compounds 5a-c are non-planar in solution and the solid-state, while 6a-c have close to planar conformations, pointing to weak hydrogen bonds between the acidic C-Hs and the adjacent azine nitrogen atoms. The cytotoxicity of the six newly synthesized and three previously prepared compounds was assessed against a human glioblastoma multiforme cell line.     

Convenient synthesis of pyrazolo[3,4-b]pyridin-3-ones and pyrazolo[3,4-b]pyridine-5-carbaldehyde using vinamidinium salts

An expedient method for the synthesis of 2-phenyl-5-aryl-2,3-dihydropyrazolo[3,4-b]pyridin-3-ones and 2-phenyl-3-oxo-2,3-dihydropyrazolo[3,4-b]pyridine-5-carbaldehyde in a single-step via condensation of vinamidinium salts with 3-amino-1-phenyl-2-pyrazolin-5-one is described.     

Reduction of indolo[2,3-b]quinoxalines

Reduction of indolo[2,3-b]quinoxalines with zinc in the presence of an anhydride gave N,N-diacyl trapped 6,11-dihydroindolo[2,3-b]quinoxalines in 43-92% yields. When the reduction with zinc was performed in TFA/TFAA, an unexpected ring opened product was isolated in 49% yield. The structure of this product could be identified as 1,2-dihydro-1-trifluoroacetyl-3-[(2-trifluoroacetylamino)phenyl]quinoxaline.     

Synthesis of 3-amino-6-methyl-5-ethoxycarbonyl-4,7-dihydrothieno[2,3-b]pyridine derivatives

The alkylation of piperidinium salts of substituted 1,4-dihydropyridine-2-thiols with chloroacetonitrile or iodoacetamide gave 2-cyanomethylthio- and 2-carbamoylmethylthio-substituted 6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-3-cyano-1,4-dihydropyridines, which undergo intramolecular cyclization in basic media to give 3-amino-6-methyl-4-aryl(pyridyl)-5-ethoxycarbonyl-2-cyano(carbamoyl)-4,7-dihydrothieno[2,3-b]pyridines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 124–128, January, 1987.     

Improved modular synthesis of thieno[3,2-b]pyrroles and thieno[2,3-b]pyrroles

A convenient modular synthesis for the construction of densely functionalized thieno[3,2-b]pyrroles, allosteric inhibitors of the Hepatitis C virus NS5B polymerase, is described. The route allows the introduction of substituents in positions 4, 5, and 6 of the thienopyrrole scaffold and can also be applied to the regioisomeric thieno[2,3-b]pyrrole core.     

Synthesis of 4-aryl-3-methyl-6-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-5-carbonitrile via a one-pot, three-component reaction

A one-pot, three-component condensation reaction of an aldehyde, 3-amino-5-methylpyrazole and ethyl cyanoacetate in ethanol to give 4-aryl-3-methyl-6-oxo-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine-5-carbonitriles, in high yields, at reflux, using a catalytic amount of p-toluenesulfonic acid, is described.     

An efficient ionic liquid mediated synthesis of substituted 5H[1,3]-thiazolo[2,3-b]quinazoline-3,5-(2H)-dione and 5H-thiazolo[2,3-b]quinazolin-5-one

A new, environmentally benign two-step synthesis of 5H[1,3]-thiazolo[2,3-b]quinazoline-3,5-(2H)-dione and 5H-thiazolo[2,3-b]quinazolin-5-one derivatives has been accomplished stepwise. The substituted 2-aminobenzoic acid upon condensation with thiourea in 1-butyl-3-methylimidazolium bromide at moderate temperature under nitrogen atmosphere yielded 2-thioxo-1H-4-quinazolinones. The resulting intermediate 2-thioxo-1H-4-quinazolinones, when reacted with 2-chloroethanoic acid/2-chloropropanal underwent cyclization to yield the desired product in excellent yields.     

Synthesis of 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles and features of their NMR spectra

Two different methods leading to 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles were investigated. Reactions of 3-aminocrotonirile with substituted salicylaldehydes provided 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles with the same substituent on positions 2 and 4 of the system. The reaction of 3-aminocrotonirile with variety of substituted 3-acetylcoumarins lead to 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles with different substituents on positions 2 and 4. The structures of the products were confirmed by spectroscopic methods. The presence of nitrile moiety in the structures with fixed geometry caused the highly downfield shift of the aromatic proton at position 10 in ¹H NMR spectrum. The electronic factor of the substituents caused variation of this downfield shift.     

A facile synthesis of 6-amino-2H, 4H-pyrano[2,3-F]pyrazole-5-carbonitriles in deep eutectic solvent

A convenient synthesis of 6-amino-2H,4H-pyrano[2,3-F]pyrazole-5-carbonitriles has been accomplished by one pot four-component cyclocondensation of aromatic aldehydes(1a-o) malanonitrile(2), ethyl acetoacetate(3), and hydrazine hydrate(4) in freshly prepared deep eutectic solvent, DES(choline chloride:urea). This protocol has afforded corresponding pyrano[2,3-F]pyrazoles in shorter reaction time with high yields, and it avoids the use of typical toxic catalysts and solvents.     

Synthesis of enantiopure furo[2,3-b]pyrroles

A simple method for the preparation of enantiopure furo[2,3-b]pyrroles, a rare class of concave bicyclic nitrogen and oxygen heterocycle, in promising yield has been developed. The 3-substituted pyrrolidinediones prepared from (2S,3S)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid (Garcinia acid) have been cyclized diastereo as well as enantioselectively to furo[2,3-b]pyrroles. The cyclization follows Baldwin’s rule.     

A one-pot synthesis of substituted pyrido[2,3-b]indolizines

An efficient and novel approach to the synthesis of substituted pyrido[2,3-b]indolizine-10-carbonitriles was developed. These structures are practically unavailable through previously described methods. The cascade transformation involves the reaction of α,β-unsaturated carbonyl compounds with a stable dimer prepared from 1-(cyanomethyl)pyridinium chloride. The reaction was performed under reflux conditions in ethanol/water and in the presence of sodium acetate. This procedure represents a eco-friendly regioselective approach to the pyrido[2,3-b]indolizine core structure.     

2,3-Disubstituted pyrrolo[2,3-b]quinoxalines via aminopalladation-reductive elimination

2,3-Disubstituted pyrrolo[2,3-b]quinoxalines have been prepared in good to high yield through the reaction of 2-alkynyl-3-trifluoroacetamidoquinoxalines with aryl and vinyl halides or triflates in the presence of Pd(PPh₃)₄ and K₂CO₃ in MeCN at 100 °C.     

First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino-[2,3-b]quinolines via intramolecular Friedel-Crafts reaction of Morita-Baylis-Hillman adducts

An acid-promoted intramolecular Friedel-Crafts reaction of the Morita-Baylis-Hillman adducts 3 derived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring 12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.     

Microwave-assisted synthesis of novel N-(4-phenylthiazol-2-yl)-benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides inspired by marine topsentines and nortopsentines

We report the synthesis of novel N-(4-phenylthiazol-2-yl)-substituted benzo[d]thiazole-, thiazolo[4,5-b]pyridine-, thiazolo[5,4-b]pyridine- and benzo[d]oxazole-2-carboximidamides, which were inspired by marine topsentines and nortopsentines. Condensation of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt) with various ortho-halogenated anilines, aminopyridines and aminophenols gave the corresponding aryliminodithiazoles in good to excellent yields. Copper(I)-mediated or nucleophilic-assisted cyclization of aryliminodithiazoles furnished cyano-functionalized benzo[d]thiazoles, thiazolo[4,5-b]- and thiazolo[5,4-b]-pyridines and benzo[d]oxazoles. The latter were condensed with substituted 4-phenylthiazol-2-amines to furnish twenty seven new polyaromatic carboximidamides in moderate to good yields.