Synthesis of some new bipyridines,thieno[2,3‐b]pyridines,and pyrazolo[3,4‐b]pyridines

Cyclocondensation of cyanoacetamide and cyanothioacetamide with sodium salt of 3‐hydroxy‐1‐(pyridin‐3‐yl)prop‐2‐en‐1‐one gave 6‐oxo‐[2,3′]bipyridine 5a and 6‐thioxo‐[2,3′]bipyridine 5b derivatives, respectively. Compound 5b upon treatment with different methylenes 8 gave thieno[2,3‐b]pyridines 10 . Treatment of 5b with iodomethane gave bipyridine derivative 7 , which cyclocondensed with hydrazines 11 to give pyrazolo[3,4‐b]pyridines 13 . J. Heterocyclic Chem., (2012).     

Pyridine‐2(1H)‐thiones: Versatile Precursors for Novel Pyrazolo[3,4‐b]pyridine,Thieno[2,3‐b]pyridines,and Their Fused Azines

Pyridine‐2(1H)‐thiones were prepared and reacted with several active halogenated reagents to afford novel thieno[2,3‐b]pyridines in excellent yields. Thieno[2,3‐b]pyridine‐2‐carbohydrazide derivative was prepared by the reaction of either ethyl 2‐((3‐cyanopyridin‐2‐yl)thio)acetate derivative or thieno[2,3‐b]pyridine‐2‐carboxylate derivative with hydrazine hydrate. On the other hand, the reaction of either pyridine‐2(1H)‐thione or ethyl 2‐((pyridin‐2‐yl)thio)acetate derivative with hydrazine hydrate afforded the corresponding 1H‐pyrazolo[3,4‐b]pyridine derivative. Thieno[2,3‐b]pyridine derivatives reacted with several reagents to afford the corresponding pyrimidine‐4(3H)‐ones and [1,2,3]triazin‐4‐(3H)‐one. Moreover, 2‐carbohydrazide derivative reacted with β‐dicarbonyl reagents to give 2‐((3‐methyl‐1H‐pyrazol‐1‐yl)carbonyl)thienopyridines. The structure of the target molecules is elucidated using elemental analyses and spectral data.     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

An efficient synthesis of pyrazolo[3,4‐b]pyrrolo[2,3‐d]pyridines from 5‐aminopyrazoles and cyclic β‐keto ester

5‐Chloroethylpyrazolo[3,4‐b]pyridines were synthesized by condensation of 5‐aminopyrazoles with α‐acetyl γ‐butyrolactone followed by cyclization treating with phosphorous oxychloride. 5‐Chloroethyl‐pyrazolo[3,4‐b]pyridines, thus obtained, were then converted to the corresponded tricyclic pyrazolo[3,4‐b]‐pyrrolo[2,3‐d]pyridines by treating with some primary amines.     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

Utility of Pyridine‐2(1H)‐thiones in the Synthesis of Novel Bis‐Thieno[2,3‐b]pyridines and Their Fused Azines

The starting materials pyridine‐2(1H)‐thiones are prepared and reacted with halogen‐containing reagents in ethanolic sodium acetate solution to give the corresponding 2‐S‐alkylpyridines, which cyclized upon their boiling in methanolic sodium methoxide solution at reflux to give the corresponding thieno[2,3‐b]pyridines in excellent yields. Bis (thieno[2,3‐b]pyridine‐2‐carboxamides), incorporating 2,6‐dibromophenoxy moiety, are prepared by the bis‐O‐alkylation of thieno[2,3‐b]pyridine‐2‐carboxamide derivatives. Two synthetic routes are designed to prepare the target molecules pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐ones, pyrido[3′,2′:4,5]thieno[3,2‐d][1,2,3]triazin‐4(3H)‐ones, and their bis‐analogues using thieno[2,3‐b]pyridine‐2‐carboxamides and their bis‐analogues. The structure of the target molecules is elucidated using elemental analyses as well as spectral data.     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

Alternating narrow band gap copolymers derived from indeno[1,2‐b]fluorene and thiophene‐cored‐thieno[3,4‐b]pyrazine derivatives—Synthesis,characterization and comparative studies of photochemical stability

Alternating narrow band gap (NBG) conjugated polymers derived from 6,6′,12,12′‐tetraoctylindeno[1,2‐b]fluorene (IF) and 2,3‐dimethyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DTTP), 2,3‐diphenyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DPTP) or 2,3‐dioctyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DOTP), named as PIF‐DTTP, PIF‐DPTP, and PIF‐DOTP, respectively, were synthesized by Suzuki coupling reaction and characterized. The photochemical stabilities of the copolymers and copolymer derived from IF and 5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DTP) were investigated by the UV absorptions, PL spectra, FT‐IR spectra, and photovoltaic properties of the copolymers as a function of UV irradiation time. The studies revealed that the degradation of thieno[3,4‐b]pyrazine (TP) ring under UV irradiation can be retarded or eliminated by introducing phenyl group into the 2,3‐positions of TP ring, and indicated that 2,3‐diphenylthieno[3,4‐b]pyrazine could be used as durable electron deficient moiety to achieve donor–acceptor NBG‐conjugated polymers. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene,thieno[3,2-b]pyridine,pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).     

Synthesis of new heteroaromatic nitrogen ligands: Pyrimido‐[4″,5″:4′,5′]‐thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidines and 1,2,3‐triazine[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]‐1,2,3‐triazines

An efficient one‐pot access for the synthesis of the previously unreported tetracyclic fused pyrimido‐[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidine ( 3 ) and 1,2,3‐triazine[4″,5″:4′,5′]thieno‐[3′,2′:4,5]thieno‐[3,2‐d]‐1,2,3‐triazine ( 5 ) heteroaromatic nitrogen ligands is described. The title compounds 3 and 5 were obtained from 3,4‐diaminothieno[2,3‐b]thiophene‐2,5‐dicarbonitrile and phosgeniminium chloride and sodium nitrite/HCl, respectively. Substituted condensed thieno[2,3‐b]thiophene derivatives 4 and 6 were synthesized by nucleophilic displacement of the chloroderivatives 3 and 5 .     

Synthesis and transformations of 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines

Reactions of 2,5-dimethoxytetrahydrofuran with 3-aminothieno[2,3-b]pyridines afford a number of substituted 3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridines. The possibility of the reaction and the yield of the product are determined by the character of a substituent in position 2 of thieno[2,3-b]pyridine. The Curtius rearrangement of 2-acylazido-3(1H-pyrrol-1-yl)thieno[2,3-b]pyridines yields 4,5-dihydropyrido[3",2":4,5]thieno[2,3-e]pyrrolo[1,2-a]pyrazin-4-ones. The molecular and crystal structures of ethyl 4-methoxymethyl-6-methyl-3-(1H-pyrrol-1-yl)thieno[2,3-b]pyridine-2-carboxylate were determined by X-ray diffraction analysis.     

Polycyclic N‐Heterocyclic Compounds,Part 69: Synthesis of 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and their transformations to related compounds

Reaction of 3‐(3‐cyanopropoxy)[1]benzofuran‐2‐carbonitriles with potassium tert‐butoxide gave 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and 5‐amino‐2,3‐dihydro[1]benzofuro[3,2‐b]oxepin‐4‐carbonitriles as new ring systems. Reactions of the 5‐chloro derivative, obtained from 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridine, produced a dihydrofuran ring‐opened compound and 5‐substituted compounds. J. Heterocyclic Chem.,(2011).     

Synthesis of trifluoromethylated pyrido[2,3‐d]pyrimidine‐2,4‐diones from 6‐aminouracils and trifluoromethylated pyrazolo[3,4‐b]‐pyridines from 5‐aminopyrazoles

5 or 7‐Trifluoromethyl‐1,2,3,4‐tetrahydropyrido[2,3‐d]pyrimidine‐2,4‐diones 3 , 5 , 10 , 13 and 4‐ or 6‐trifluoromethylpyrazolo[3,4‐b]pyridines 15 , 16 , 19 , 21 were prepared from 6‐aminouracils and 5‐aminopyrazoles, respectively, in good yields by the use of building blocks such as 4,4,4‐trifluoro‐1‐phenyl‐1,3‐butanedione, 1,1,1‐trifluoro‐4‐phenyl‐3‐buten‐2‐one, 4‐ethoxy‐1,1,1‐trifluoro‐3‐buten‐2‐one, and ethyl trifluoroacetoacetate.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

New method for the synthesis of substituted thieno[3,2-b]pyridines and 5H-pyrano[2,3-d]thieno[3,2-b]pyridines derived from them

A new highly selective method was developed for the synthesis of substituted thieno[3,2-b]-pyridines based on the domino reaction of monopotassium salt (rather than dipotassium one) of carbamoylcyanodithioacetic acid with ethyl 4-chloroacetoacetate. Substituted 5H-pyrano[2,3-d]-thieno[3,2-b]pyridines were synthesized based on these thieno[3,2-b]pyridines.     

Synthesis of condensed tricyclic pyrazolo[3,4-b]thieno[2,3-d]pyridine and related isostere derivatives

In this paper we report the synthesis of an isosteric series of new heterotricyclic derivatives, corresponding to pyrazolo[3,4-b]thieno[2,3-d]pyridine ( 1 ), pyrazolo[3,4-b]furano[2,3-d]pyridine ( 2 ) and pyrazolo[3,4-b]pyrrolo[2,3-d]pyridine ( 3 ). These functionalized compounds were obtained, in high overall yield, by an ‘one-pot’ reaction of the chloroester intermediate 4 , possessing the pyrazolo[3,4-b]pyridine system, with an adequate α-hetero-acetyl ester derivative, in SNAr/Dieckman cyclization type consecutive reactions.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 24 [1]. Synthesis of imidazo[1,5‐d]thieno[2,3‐b][1,4]‐thiazine derivatives as potential receptor ligands

A facile synthesis of the imidazo[1,5‐d]thieno[2,3‐b][1,4]thiazine ring system is described. Reaction of 6‐benzyl‐2,3‐dihydro‐1H‐thieno[2,3‐b][1,4]thiazine‐2‐one ( 1 ) with potassium tert‐butoxide and diethylchlorophosphate gave intermediate 2 which resulted in the disired ring system after adding the corresponding isocyanides and potassium tert‐butoxide.     

Green One‐Pot Solvent‐Free Synthesis of Pyrazolo[1,5‐a]pyrimidines,Azolo[3,4‐d]pyridiazines,and Thieno[2,3‐b]pyridines Containing Triazole Moiety

Synthesis of pyrazolo[1,5‐a]pyrimidines, [1,2,4]triazolo[1,5‐a]pyrimidine, 8,10‐dimethyl‐2‐(5‐methyl‐1‐phenyl‐4,5‐dihydro‐1H‐1,2,3‐triazol‐4‐yl)pyrido[2′,3′:3,4]‐pyrazolo[1,5‐a]pyrimidine, benzo[4,5]imidazo[1,2‐a]pyrimidine via heterocyclic amines, and sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one were carried out. Also, synthesis of isoxazoles, and pyrazoles from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐triazole‐4‐yl)prop‐2‐en‐1‐one and hydroxymoyl chlorides and hydrazonoyl halides, respectively, were made. Analogously, (1,2,3‐triazol‐4‐yl)thieno[2,3‐b]pyridine derivatives were obtained from sodium 3‐hydroxy‐1‐(5‐methyl‐1‐phenyl‐1H‐1,2,3‐ triazole‐4‐yl)prop‐2‐en‐1‐one and cyanothioacetamide followed by its reacting with active methylene compounds. In addition to full characterization of all synthesized compounds, they were tested to evaluate their antimicrobial activities, and some compounds showed competitive activities to those of tetracycline, the typical antibacterial drug, and clotrimazole, the typical antifungal drug.     

1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine and its derivatives

The synthesis of the parent ring system and some of the derivatives of 1H-pyrazolo[3,4-d]thieno[2,3-b]pyridine are described.     

An Efficient Synthesis and Fluorescent Properties of Pyrazole[3,4‐b]thieno[2,3‐e]pyridine Derivatives

A simple and efficient method for the synthesis of pyrazole[3,4‐b]thieno[2,3‐e]pyridine derivatives via the sequence of three‐component, catalyst‐free, and solvent‐free condensation and oxidation was described. The products feature a donor‐π‐conjugated acceptor fluorescent activity system, and the fluorescence emission wavelength was measured in methanol. Some products were fluorescent in solution emitting at blue light (λ_em = 430–505 nm).