Reactions of hydrazonoyl halides 43 : Synthesis of some new 2,3‐dihydro‐1,3,4‐thiadiazoles,pyrazoles, pyrazolo[3,4‐d]‐pyridazines,thieno[2,3‐b]pyridines,pyrimidino[4′,5′:4,5]thieno[2,3‐b]‐pyridines and pyrrolo[3,4‐d]pyrazoles

2,3‐Dihydro‐1,3,4‐thiadiazoles, pyrazoles, pyrazolo[3,4‐d]pyridazines, thieno[2,3‐b]pyridines, pyrim‐idino[4′,5′:4,5]thieno[2,3‐b]pyridines and pyrrolo[3,4‐d]pyrazoles were obtained in a good yields by treatment of hydrazonoyl halides with each of alkyl carbodithioates, 3‐(dimethylamino)‐1‐naphtho[1,2‐d]furan‐2‐ylprop‐2‐en‐1‐one and N‐arylmalemides.     

Synthesis of novel pyrido[3′,2′:5,6]thiopyrano[3,2‐b]indol‐5(6H)‐ones and 6H‐pyrido[3′,2′:5,6]thiopyrano[4,3‐b]quinolines,two new heterocyclic ring systems

The synthesis of new pyrido[3′,2′:5,6]thiopyrano[3,2‐b]indol‐5(6H)‐ones was accomplished by the Fischer‐indole cyclization of some 2,3‐dihydro‐3‐phenylhydrazonothiopyrano[2,3‐b]pyridin‐4(4H)‐ones, obtained from the 2,3‐dihydro‐3‐hydroxymethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐one, by the Japp‐Klingemann reaction. 6H‐Pyrido[3′,2′:5,6]thiopyrano[4,3‐b]quinolines were obtained by reaction of 2,3‐dihydrothiopyrano‐[2,3‐b]pyridin‐4(4H)‐ones with o‐aminobenzaldehyde or 5‐substituted isatins. The preparation of some derivatives, functionalized with an alkylamino‐substituted side chain, is also described.     

Synthesis of some pyrimido[4′,5′:4,5]thieno[2,3-b]quinolines and related heterocycles

Several thieno[2,3-b]quinolines 6a-i have been synthesized. These compounds were used as key intermediates in the synthesis of oxazino[4′,5′:4,5]thieno[2,3-b]quinoline 8 , pyrimido[4′,5′:4,5]-thieno[2,3-b]quinolines 9–12 , triazino[4′,5′:4,5]thieno[2,3-b] quinolines 14 and imidazo[4′,5′:4,5]-thieno[2,3-b]quinolines 17 .     

Synthesis of New Pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline Derivatives in One Step

As a continuation of our search for new heterocyclic compounds, the synthesis of pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxaline ring system is described. A series of new derivatives of this heterocyclic system ( 3a–d ) have been synthesized through the one‐pot heterocyclization of the appropriate 5‐amino6‐methylpyrimidine‐4‐thiols and 2,3‐dichloroquinoxaline in the presence of K₂CO₃ in dimethylformamide under reflux. N‐alkylation of the synthesized compounds with alkyl halides in KOH/dimethylformamide also gave the desired new derivatives of N‐alkylated pyrimido[5′,4′:5,6][1,4]thiazino[2,3‐b]quinoxalines ( 4a–h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical 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.     

Ring closure reactions of pyrido[2,3‐d]pyrimidines to pyrano[2′,3′:4,5]‐ and oxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines

The cyclocondensation of 5‐hydroxy‐pyrido[2,3‐d]pyrimidines 1 with malonates gives pyrano[2′,3′:4,5]‐pyrido[2,3‐d]pyrimidines 2 . Nitration of 1 and reduction with zinc in the presence of carboxylic acids/anhydrides gave 2‐alkyloxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines 4 , which were ring‐opened to 6‐aminopyrido[2,3‐d]pyrimidines 5, 6 and 7 . Cyclization of 6‐aminopyrido[2,3‐d]pyrimidines 6 with benzoylchlorides 8 gave 2‐aryloxazolo[5′,4′:4,5]pyrido[2,3‐d]pyrimidines 9 . Reaction conditions for the cyclization have been studied by differential scanning calorimetry (DSC).     

An Efficient One‐pot Synthesis of Novel Spiro Cyclic 2‐Oxindole Derivatives of Pyrimido[4,5‐b]Quinoline,Pyrido[2,3‐d:6,5‐d′]Dipyrimidine and Indeno[2′,1′:5,6]Pyrido [2,3‐d]Pyrimidine in Water

A novel and facile one‐pot synthesis of spiro cyclic 2‐oxindole derivatives of pyrimido[4,5‐b]quinoline‐4,6‐dione, pyrido[2,3‐d:6,5‐d′]dipyrimidine‐2,4,6‐trione, and indeno[2′,1′:5,6]pyrido [2,3‐d]pyrimidine employing 6‐aminothiouracil (or 6‐aminouracil), isatin, and cyclic 1,3‐diketone (e.g. 1,3‐indanedione, dimedone, or barbituric acid) has been developed.     

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyrimido[4′,5′:4,5]theino[2,3-b]quinoline and pyrido[1′,2′:1,2]pyrimido[4,5-b]quinoline

Syntheses of substituted pyrazolo[3,4-b]quinolines, 3,4-dihydro-4-oxopyriraido[4′,5′:4,5]theino[2,3-b]quinoline and 12-phenylpyrido[1′,2′:1,2[pyrimido[4,5-b]quinoline are described.     

One‐pot Sequential Reactions Featuring a Copper‐catalyzed Amination Leading to Pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines and Dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines

Tetracyclic skeletons combining an imidazo[1,2‐a]pyridine moiety with a quinoline framework such as pyrido[2′,1′:2,3]imidazo[4,5‐b]quinoline are stimulating increasing interests since they are close isosteres of a series of powerful antiproliferative compounds. In this paper, we report a novel methodology for the synthesis of pyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines through one‐pot sequential reactions of commercially available or readily obtainable 2‐aminopyridines, 2‐bromophenacyl bromides, aqueous ammonia, and aldehydes. Moreover, dihydropyrido[2′,1′:2,3]imidazo[4,5‐c]quinolines could also be obtained in a similar manner by using various ketones as the substrates in place of aldehydes. Notably, the whole procedure combines condensation/amination/cyclization reactions in one pot to give complex compounds in a simple and practical manner. Compared with literature methods, the synthetic strategy reported herein has the advantages of readily available starting materials, structural diversity of products, good functional group tolerance, and obviation of step‐by‐step operations.     

A Straightforward Approach for the Synthesis of Novel Derivatives of Benzo[b]pyrazolo[5′,1′:2,3]pyrimido[4,5‐e][1,4]thiazine

Several derivatives of the novel benzo[b]pyrazolo[5′,1′:2,3]pyrimido[4,5‐e][1,4]thiazine ring system have been synthesized through the one‐pot cyclocondensation of 6‐bromo‐7‐chloro‐2‐(ethylthio)‐5‐methylpyrazolo[1,5‐a]pyrimidine‐3‐carbonitrile ( 4 ) with o‐aminothiophenol in the presence of Et₃N in CH₃CN. The true regio isomer ( 5 ) was also determined by X‐ray crystallographic analysis. The N‐alkylation of the synthesized compound ( 5 ) was also accomplished.     

Synthesis of 3‐substituted pyrido[4′,3′:4,5]thieno[2,3‐d]pyrimidines and related fused thiazolo derivatives

Convenient syntheses of 3‐substituted ethyl 4‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrid[4′,3′:4,5]thieno[2,3‐d]pyrimidine‐7‐carboxylates 3a, b, 6, 11–13 , ethyl 3‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5 H‐pyrido[4′,3′:4,5]thieno[2,3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8‐7H‐carboxylate ( 4 ), and ethyl 2‐methyl‐5‐oxo‐2,3,6,9‐tetrahydro‐5H‐pyrido[4′,3′:4,5]thieno[2, 3‐d][1,3]thiazolo[3,2‐a]pyrimidine‐8[7H]carboxylate ( 8 ) from diethyl 2‐isothiocyanato‐4,5,6,7‐tetrahythieno[2,3‐c]pyridine‐3,6‐dicarboxylate ( 1 ) are reported. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:201–207, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10131     

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 .     

The synthesis of monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines

A series of monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines has been prepared by photocyclization of the appropriate N-methoxyphenyl-1-chloronaphtho[2,1-b]thiophene-2-carboxamides. Some of the lactams obtained were converted into the thiolactams and their S-methyl derivatives. The lactams were also converted into the corresponding 6-chloro derivatives. Some of these were catalytically dechlorinated into the monomethoxynaphtho[1′,2′:4,5]thieno[2,3-c]quinolines which were then quaternized into the N-methyl quaternary salts.     

Syntheses of 8-aminoimidazo[4′,5′:5,6]pyrido[2,3-d]pyrimiciines: Linear tricyclic analogs of adenine

The syntheses of 8-aminoimidazo[4′,5′:5,6]pyrido[2,3-d]pyrimidines (7), stretched-out versions of the naturally occuring nucleoside base adenine, are reported. Their preparation involves conversion of purine into 5-arninoimidazo[4,5-b]pyrimidine-6-carbonitrile ( 1 ) by reaction with malononitrile, followed by construction of the pyrimidine ring in two steps via the ethoxymethylene derivative 3 . 8-Azapurine can be converted to 8-amino-1,2,3-triazolo[4′,5′:5,6]pyrido[2,3-d]pyrimidines 8 in a similar fashion.     

1H and 13C spectral assignment of naphtho[2′,1′:5,6]‐naphtho[2′,1′:4,5]thieno[2,3‐c]quinoline using the IDR‐GHSQC‐TOCSY experiment

The assignment of the NMR spectra of the polynuclear heteroaromatic naphtho[2′,1′:5,6]naphtho‐[2′,1′:4,5]thieno[2,3‐c]quinoline is reported. The analysis was based on the homonuclear ROESY, heteronuclear direct GHSQC, IDR‐GHSQC‐TOCSY, and long‐range GHMBC experiments. The complete ¹H and ¹³C shift assignments are reported.     

Synthesis of 1,2,3,4,4a,5-hexahydropyrido[1′,2′:4,5][1,4]oxazino[2,3-b]quinoxaline derivatives

Reactions of 2,3-dichloroquinoxalines with 2-(hydroxymethyl)piperidine resulted in a series of 1,2,3,4,4a,5-hexahydropyrido[1′,2′:4,5][1,4]oxazino[2,3-b]quinoxaline derivatives. The structures of the products were confirmed by nmr and x-ray crystallography.     

Synthesis and Antioxidant Evaluation of Quinoxalino[2′,3′:5,6][1,3,4]thiadiazino[2,3‐b]quinazolin‐15‐ones: Derivatives of a Novel Ring System

Quinoxalino[2′,3′:5,6][1,3,4]thiadiazino[2,3‐b]quinazolin‐15‐one, a novel fused heterocyclic system, was synthesized from a one‐pot condensation reaction of 2,3‐dichloroquinoxaline and 3‐amino‐2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one under mild condition. Derivatization was performed on treatment of the titled compound with several alkyl bromides. In vitro antioxidant activity of the synthesized compounds was evaluated.     

Synthesis of 7,8,9,10-tetrahydropyrido[3′,4′:4,5]pyrrolo[2,3-c]quinolines

A series of structurally novel 7,8,9,10-tetrahydropyrido[3′,4′:4,5]pyrrolo[2,3-c,]quinolines, 4a-c , were synthesized via a facile Fischer indole cyclization from the appropriately substituted hydrazinoquinolines 2a-c . Acetamides 4a,c were hydrolyzed to 5a,b and further converted to tertiary amines 6a-c . Potent antihypertensive activity has been observed with a number of the title compounds as well as the intermediate 3a .     

An Efficient synthesis of pyrimido[4,5‐b]quinoline and indeno[2′,1′:5,6]pyrido[2,3‐d]pyrimidine derivatives via multicomponent reactions in ionic liquid

A series of pyrimido[4,5‐b]quinoline and indeno[2′,1′:5,6]pyrido[2,3‐d]pyrimidine derivatives were synthesized via the three‐component reaction of an aldehyde, 6‐aminopyrimidine‐2,4‐dione and 5,5‐dimethyl‐1,3‐cyclohexanedione or 1,3‐indanedione in ionic liquid 1‐n‐butyl‐3‐methylimidazolium bromide ([bmim]Br). This protocol has the advantages of easier work‐up, milder reaction conditions, high yields and an environmentally benign procedure compared with other methods.     

Synthesis and total 1H-NMR assignment of naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]-thieno[2,3-c] [1,10]phenanthroline

Naphtho[1′,2′:4,5]thieno[2,3-c][1,10]phenanthroline and naphtho[2′,1′:4,5]thieno[2,3-c][1,10]phenanthroline, two novel polycyclic heterocyclic ring systems, have been synthesized in four steps from known starting materials. The total ¹H nmr spectral assignments were made using a COSY experiment to identify the spin systems.