Utilization of cleavage of the [1]benzofuro[2,3‐e][1,2,4]triazine ring for the synthesis of oxygen,nitrogen and sulfur derivatives of [1,2,4]triazine

A series of 6‐azacytosines 4a‐4k and 5a‐5c were prepared by nucleophilic cleavage of furan ring of [1]benzofuro[2,3‐e][1,2,4]triazine derivative 1 . Some of them were used for the preparation of derivatives of [1,2,4]triazolo[4,3‐d][1,2,4]triazine ( 6a‐6d ) and tetrazolo[1,5‐d][1,2,4]triazine (7). The reaction of 1 with hydrogen sulfide afforded the corresponding 6‐(2‐hydroxyphenyl)‐2‐phenyl‐5‐thioxo‐4,5‐dihydro‐1,2,4‐tri‐azin‐3(2H)‐one ( 8 ), while with hydrogen selenide 6‐(2‐hydroxyphenyl)‐2‐phenyl‐4,5‐dihydro‐1,2,4‐triazin‐3(2H)‐one ( 9 ) was formed. The prepared compounds were tested for biological activity.     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

Synthesis and Functionalization of 8‐Methyl‐2h‐pyrimido [2,1‐c][1,2,4]triazine‐3,6(1h,4h)‐dione

6‐Methyl‐2‐methylthio‐4‐oxopyrimidin‐3(4H)‐yl)acetohydrazide on heating in benzylamine undergo cyclization to 8‐methyl‐2H‐pyrimido[2,1‐c][1,2,4]triazine‐3,6(1H, 4H)‐dione, which under treatment with bromine in glacial acetic acid was converted to 7‐bromo substituted derivative and at reflux with Lawesson's reagent yielded 3‐thioxo compound. The latter reacted with primary and secondary amines to give 3‐amino substituted pyrimidotriazines and on alkylation—the corresponding S‐alkyl derivatives.     

Synthesis of some new five membered heterocycles,a facile synthesis of oxazolidinones

The synthesis and structural properties of two kinds of thiosemicarbazide derivatives ( 2a‐c and 3a‐c ) and one kind of semicarbazide derivatives ( 4a, 4b ) have been described. These compounds were synthesized by treating 2‐(4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl)acetohydrazides ( 1a‐c ) with benzyl isothiocyanate, 3‐florophenyl isothiocyanate and benzylisocyanate, respectively. The synthesis of 4‐amino‐3‐alkyl‐1‐[(4‐alkyl‐5‐mercapto(or 5‐oxo)‐4H‐1,2,4‐triazol‐3‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 5a‐c, 6a‐c and 7 ) have been performed from the reaction with sodium hydroxide. On the other hand, the acidic treatment of compounds 2b, 3b and 4b has afforded 4‐amino‐3‐(4‐chlorobenzyl)‐1‐[(5‐alkylamino‐1,3,4‐thidazol(or 1,3,4‐oxazol)‐2‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 8, 9 and 10 ). The condensation of thiosemi(or semi)carbazide derivatives ( 2a‐c, 3c and 4b ) with 4‐chlorophenacylbromide have resulted in the formation of 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐(3,4‐dialkyl‐1,3‐thiazol(or oxazol)‐2(3H)‐yliden]acetohydrazides ( 11a‐c, 12, 13 ), while their condensation with chloroacetic acid has produced 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐[3‐(3‐alkyl)]‐4‐oxo‐1,3‐thiazolidin(or oxazolidin)‐2‐yliden}acetohydrazides ( 14, 15 and 16 ). The spectral data and elemental analyses have support the proposed structures.     

Synthesis and reactions of 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]‐quinazolin‐9‐one and 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one

The reaction of 3‐N‐(2‐mercapto‐4‐oxo‐4H‐quinazolin‐3‐yl)acetamide ( 1 ) with hydrazine hydrate yielded 3‐amino‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 2 ). The reaction of 2 with o‐chlorobenzaldehyde and 2‐hydroxy‐naphthaldehyde gave the corresponding 3‐arylidene amino derivatives 3 and 4 , respectively. Condensation of 2 with 1‐nitroso‐2‐naphthol afforded the corresponding 3‐(2‐hydroxy‐naphthalen‐1‐yl‐diazenyl)‐2‐methyl‐3H‐[1,2,4]triazolo[5,1‐b]quinazolin‐9‐one ( 5 ), which on subsequent reduction by SnCl₂ and HCl gave the hydrazino derivative 6. Reaction of 2 with phenyl isothiocyanate in refluxing ethanol yielded thiourea derivative 7. Ring closure of 7 subsequently cyclized on refluxing with phencyl bromide, oxalyl dichloride and chloroacetic acid afforded the corresponding thiazolidine derivatives 8, 9 and 10 , respectively. Reaction of 2‐mercapto‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 11 ) with hydrazine hydrate afforded 2‐hydrazino‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 12 ). The reactivity 12 towards carbon disulphide, acetyl acetone and ethyl acetoacetate gave 13, 14 and 15 , respectively. Condensation of 12 with isatin afforded 2‐[N‐(2‐oxo‐1,2‐dihydroindol‐3‐ylidene)hydrazino]‐3‐phenylamino‐3H‐quinazolin‐4‐one ( 16 ). 2‐(4‐Oxo‐3‐phenylamino‐3,4‐dihydroquinazolin‐2‐ylamino)isoindole‐1,3‐dione ( 17 ) was synthesized by the reaction of 12 with phthalic anhydride. All isolated products were confirmed by their ir, ¹H nmr, ¹³C nmr and mass spectra.     

Glycosylation of 4‐Aryl‐1‐thioxo[1,2,4] triazolo[4,3‐a] quinazolin‐5(4H)‐one

Reaction of 4‐aryl‐1‐thioxo [1,2,4] triazolo [4,3‐a] quinazolin‐5 (4H)‐ones (2a,b) with acetylated glycosyl bromides 3a–c under alkaline conditions afforded the corresponding S‐glycoside derivatives 4, 5 and N‐glycoside derivatives 6, 7. Oxidation of S‐glycosyl derivatives 4, 5 with m‐chloroperbenzoic acid yielded the corresponding sulphones 8, 9, whereas the N‐glycosyl derivatives 6, 7 yielded 1‐oxo derivatives 10, 11. However their O‐deacetylation with sodium methoxide in methanol caused cleavage of the S‐glycosyl residue and gave N ²‐glycosylated analogues 12, 13, 14 and 15.     

Synthesis of New Azocompounds and Fused Pyrazolo[5,1‐c][1,2,4]triazines Using Heterocyclic Components

Diazotization of 3‐methyl‐4‐phenyl‐1H‐pyrazol‐5‐amine 1 in hydrochloric acid has been reported to afford the corresponding diazonium salt 2 . The latter underwent azocoupling with a variety of active methylene compounds (barbituric 3a and thiobarbituric 3b acid, 2‐hetarylpyrimidine‐4,6‐dione 6a , 6b , 4‐hydroxy‐6‐methylpyridin‐2(1H)‐one 10a , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one 10b , 4‐hydroxy‐1‐p‐tolyl‐1H‐pyrazole‐3‐carboxylic acid ethyl ester 14 , 1,3‐thiazolidine‐2,4‐dione 16a , 2‐thioxo‐1,3‐thiazolidin‐4‐one 16b ) to yield new pyrazolylazo derivatives. Fused pyrazolo[5,1‐c][1,2,4]triazines 5 , 9a , 9b , 12 , 13 were obtained by heterocyclization reactions. Copyright © 2013 HeteroCorporation     

New One Pot‐synthesis of Functionally Substituted Pyridines from Enaminoketones

Several new pyridine derivatives were prepared via reaction of enaminoketones 1a , 1b , 1c , 1d with active hydrogen reagents. Reaction of the enaminoketones 1a , 1b , 1c with 4‐acetyl‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one 2a yielded the pyridines 3a , 3b , 3c . Condensation of the enaminonitrile 1d with compounds 2b , 2c , 2d and compound 8 gave the pyridine derivatives 6a , 6b , 6c and 10 respectively. Also, (3‐(dimethylamino)acryloyl)‐2H‐chromen‐2‐one 1a reacted with active methylenes in diethyl 3‐oxopentanedioate 12 and 4‐methyl‐6‐oxo‐2‐thioxo‐1,2,5,6‐tetrahydropyridine‐3‐carbonitrile 15 to afford the pyridine derivatives 14 and 16 respectively.     

Aromatization and ring cyclization: A reasonable understanding on the ring cyclization mechanism of 3‐amino‐6‐hydrazino‐1,2,4‐triazin‐5(2H)‐one reacted with one‐carbon fragment reagents or nitrous acid

The cyclization mechanism for the title compound ( 2 ) reacting with one‐carbon fragment reagents or nitrous acid to afford heterobicyclic compounds 6‐amino‐3‐substituted‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐ones ( 3a～d ) or 6‐amino‐1,2,3,4‐tetrazolo[5,1‐f][1,2,4]triazin‐8(7H)‐one ( 4 ), respectively, is explored in this paper. When 3‐amino‐2‐benzyl‐6‐hydrazino‐1,2,4‐triazin‐5(2H)‐one ( 10 ), the N‐2 benzylated derivative of 2 , is treated under the same conditions, ring cyclization does not occur; instead, 3‐amino‐2‐benzyl‐6‐substituted‐1,2,4‐triazin‐5(2H)‐ones ( 11,12,14 ) and 2‐N‐(2‐amino‐1‐benzyl‐4‐oxo‐1,2,4‐triazin‐5‐yl)semicarbazide ( 13 ) are formed. Alternatively, when 3‐amino‐6‐hydrazino‐2‐[(2‐hydroxyethoxy)methyl]‐1,2,4‐triazin‐5(2H)‐one ( 16 ), a compound bearing the 2‐[(2‐hydroxyethoxy)methyl] side‐chain at N‐2 of 2 by an N? C? O bond, reacts with glacial acetic acid or nitrous acid, the side‐chain is cleaved through acidolysis to affford the ring‐closed compound 6‐amino‐3‐methyl‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐one ( 3b ) or compound 4 , respectively. From these results, we suggest a cyclization mechanism that the ring cyclization is dependent on the aromatization of the 1,2,4‐triazine ring, which influence the reactivity and reaction behavior of the π‐deficient 1,2,4‐triazine.     

Enaminone Incorporating a Dibromobenzofuran Moiety: Versatile Precursor for Novel Azines and Azolotriazines

2‐Acetyl‐5,7‐dibromobenzo[b]furan ( 1 ) reacted with dimethylformamide‐dimethylacetal to give the corresponding (E)‐enaminone 3 which coupled with aromatic diazonium chloride to afford the corresponding key intermediates 3‐oxo‐2‐(2‐arylhydrazono)propanals 6a , b . Compounds 6a , b were used to prepare novel 3‐imino‐2,3‐dihydropyridazines 10a , b and 6‐phenylazopyrido[2,3‐d]pyrimidin‐4(1H)‐one derivatives 15a , b through their reaction with acetonitrile derivatives 8a , b and 6‐aminopyrimidin‐4(1H)‐one 13 , respectively. On the other hand, the enaminone 3 was taken as a synthetic precursor to synthesize novel pyrazolo[5,1‐c][1,2,4]triazines 21a – c , [1,2,4]triazolo[3,4‐c][1,2,4]triazines 25 and benzimidazo[2,1‐c][1,2,4]triazine 29 containing 5,7‐dibromobenzofuran‐2‐oyl moiety via its coupling with the appropriate diazonium salts of a variety of hetero‐armomatic amines in a facile one‐step route.     

Utility of Enaminonitriles in Heterocyclic Synthesis: Synthesis of Some New Pyrazole,Pyridine, and Pyrimidine Derivatives

The starting (1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)carbonohydrazonoyl dicyanide ( 2 ) was used as key intermediate for the synthesis of 3‐amino‐2‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐ylazo)‐[3‐substituted]‐1‐yl‐acrylonitrile derivatives ( 3 – 10 ). In addition, nitrile derivative 2 reacted with hydrazine hydrate or malononitrile to afford the corresponding 3,5‐diaminopyrazole 11 and enaminonitrile derivative 13 , respectively. On the other hand, compound 3 was subjected to react with malononitrile, acetic anhydride, triethylorthoformate, N,N‐dimethylformamide (DMF)‐dimethylacetal, thiourea, and hydroxylamine hydrchloride to afford antipyrine derivatives 16 – 21 . Moreover, the reaction of enaminonitrile 3 with carbon disulfide in pyridine afforded the pyrimidine derivative 22 , whereas, in NaOH/DMF followed by the addition of dimethyl sulphate afforded methyl carbonodithioate 24 . The reaction of enaminonitrile derivatives 3 – 5 with phenylisothiocyanate afforded the thiopyrimidine derivatives 25a – c . Finally, the enaminonitrile 4 reacted with 3‐(4‐chloro‐phenyl)‐1‐phenyl‐propenone to afford the pyridine derivative 27 . The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹³C‐NMR, ¹H–NMR, and MS).     

Synthesis of some novel pyrazolo[1,5‐a]pyrimidine, 1,2,4‐triazolo[1,5‐a]pyrimidine,pyrido[2,3‐d]pyrimidine,pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives incorporating a thiazolo[3,2‐a]benzimidazole moiety

E‐3‐(N,N‐Dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one ( 2 ) was synthesized by the reaction of 1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)ethanone ( 1 ) with dimethylformamide‐dimethylacetal. The reaction of 2 with 5‐amino‐3‐phenyl‐1H‐pyrazole ( 4a ) or 3‐amino‐1,2,4‐(1H)‐triazole ( 4b ) furnished pyrazolo[1,5‐a]pyrimidine and 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives 6a and 6b , while the reaction of enaminone 2 with 6‐aminopyrimidine derivatives 7a,b afforded pyrido[2,3‐d]pyrimidine derivatives 9a,b , respectively. The diazonium salts 11a or 11b coupled with compound 2 to yield the pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives 13a and 13b . Some of the newly synthesized compounds exhibited a moderate effect against some bacterial and fungal species.     

Chemical Reactivity of 4,9‐Dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromene‐6‐Carboxaldehyde Toward Some Nucleophilic Reagents

The chemical reactivity of 4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g ]chromene‐6‐carboxaldehyde (6‐formylkhellin) ( 1 ) was studied toward a diversity of nitrogen nucleophilic reagents. Reaction of carboxaldehyde 1 with some primary amines and heterocyclic amines afforded the corresponding Schiff bases. Also, the reactivity of carboxaldehyde 1 was studied toward some hydrazine derivatives, namely 7‐chloro‐4‐hydrazinoquinoline, 3‐hydrazino‐5,6‐diphenyl‐1,2,4‐triazine, N⁴‐phenylthiosemicarbazide, and S‐benzyldithiocarbazate. 6‐Formylkhellin ( 1 ) underwent ring transformation upon treatment with hydroxylamine hydrochloride producing 5‐hydroxy‐4,9‐dimethoxy‐7‐oxo‐7H‐furo[3,2‐g ]chromene‐6‐carbonitrile ( 22 ). Some pyrimidine, [1,2,4]triazolo[4,3‐a ]pyrimidine, tetrazolo[1,5‐a ]pyrimidine, and diazepine derivatives linked benzofuran were efficiently synthesized. Reaction of carboxaldehyde 1 with a variety of 1,4‐binucleophiles produced furochromone‐fused benzodiazepine, pyridotriazepine, benzoxazepine, and benzothiazepine derivatives. Some unsymmetrical thiocarbohydrazones were also synthesized. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Functionalized 2‐Hydrazinobenzothiazole with Isatin and Some Carbohydrates under Conventional and Ultrasound Methods and Their Biological Activities

Several chemical reactions were carried out on 3‐(benzothiazol‐2‐yl‐hydrazono)‐1,3‐dihydro‐indol‐2‐one ( 2 ). 3‐(Benzothiazol‐2‐yl‐hydrazono)‐1‐alkyl‐1,3‐dihydro‐indol‐2‐one 3a , 3b , 3c have been achieved. Reaction of compound 2 with ethyl bromoacetate in the presence of K₂CO₃ resulted the uncyclized product 4 . Reaction of compound 2 with benzoyl chloride afforded dibenzoyl derivative 5 . Compound 2 was smoothly acetylated by acetic anhydride in pyridine to give diacetyl derivative 6b . Moreover, when compound 4 reacted with methyl hydrazine, it yielded dihydrazide derivative 7 , whereas the hydrazinolysis of this compound with hydrazine hydrate gave the monohydrazide derivative 8 . {N‐(Benzothiazol‐2‐yl‐N′‐(3‐oxo‐3,4‐dihydro‐2H‐1,2,4‐triaza‐fluoren‐9‐ylidene)hydrazino]‐acetic acid ethyl ester ( 9 ) was prepared by ring closure of compound 8 by the action of glacial acetic acid. In addition, the reaction of 2‐hydrazinobenzothiazole ( 1 ) with d ‐glucose and d ‐arabinose in the presence of acetic acid yielded the hydrazones 10a , 10b , respectively. Acetylation of compound 10b gave compound 11b . On the other hand, compound 13 was obtained by the reaction of compound 1 with gama‐d ‐galactolactone ( 12 ). Acetylation of compound 13 with acetic anhydride in pyridin gave the corresponding N¹‐acetyl‐N²‐(benzothiazolyl)‐2‐yl)‐2,3,4,5,6‐penta‐O‐acetyl‐d ‐galacto‐hydrazide ( 14 ). Better yields and shorter reaction times were achieved using ultrasound irradiation. The structural investigation of the new compounds is based on chemical and spectroscopic evidence. Some selected derivatives were studied for their antimicrobial and antiviral activities.     

Unexpected Formation of Thioglycolurils Precursors

Unexpectedly, nitrosation of 5,7‐dialkyl‐3‐thioxoperhydroimidazo[4,5‐e]‐1,2,4‐triazine‐6‐ones(thiones) with sodium nitrite in glacial AcOH led to 3,3′‐bis(5,7‐dialkyl‐1‐nitroso‐6‐oxo(thioxo)‐1,4,4a,5,7,7a‐hexahydroimidazo[4,5‐e]‐1,2,4‐triazinyl)disulfides that decomposed spontaneously into 1,3‐dialkyl‐5‐thioxohexahydroimidazo[4,5‐d]imidazol‐2(1H)‐ones(thiones) in DMSO‐d₆ in the presence of water.     

Synthesis of 3‐(4‐Oxo‐4H‐quinolizinyl‐3) and 3‐(4‐Oxo‐4H‐pyridino[1,2‐a]pyrimidinyl‐3) substituted lactic acid derivatives

A one‐step ‘ring switching’ transformation of (S)‐3‐[(dimethylamino)methylidene]‐5‐(methoxycarbonyl)tetrahydrofuran‐2‐one ( 4 ) with 2‐pyridineacetic acid derivatives ( 5–7 ) and 2‐aminopyridines ( 8, 9 ) afforded the corresponding 3‐(4‐oxo‐4H‐quinolizinyl‐3)‐ (15–17) and 3‐(4‐oxo‐4H‐pyridino[1,2‐a]pyrimidinyl‐3)‐2‐hydroxypropanoates ( 18, 19 ), respectively.     

Antimicrobial Properties of Some New Synthesized Benzothiazole Linked Carboxamide,Acetohydrazide, and Sulfonamide Systems

We report herein the interaction of diethylethoxymethylene malonate ( 1 ) with 2‐cyanomethylbenzothiazole ( 7 ) to give diethyl 2‐(2‐benzothiazole‐2‐(3H)‐ylidiene)‐2‐(cyano ethyl) malonate ( 8a ) in excellent yield. Ethyl 4‐cyano‐1‐oxo‐1H‐benzo[4,5]thiazolo[3,2‐a]pyridine‐2‐carboxylate (9) was synthesized from 8a and subjected to react with hydrazine hydrate to give its corresponding acid hydrazide 10 . Condensation of 10 with different acid anhydrides afforded the corresponding benzothiazolo pyridine carboxamide derivatives 11 – 15 . In addition, we report a simple synthesis of N′‐(benzo[d]thiazol‐2‐yl)‐2‐((4‐ayl)amino)acetohydrazide derivative ( 17 ), which then reacted with different amines to give the corresponding acetohydrazide derivatives 19a – c . Moreover, compound 17 reacted with some sulfonamide derivatives to give the corresponding sulfonamide derivatives 20 and 22a , b .The newly synthesized compounds were established their structures on the bases of their correct analytical and spectral data and evaluated their antimicrobial activity. It was found that compounds 22a , b displayed the highest antimicrobial activity against the tested organisms.     

Synthesis of some new Pyridine‐based Heterocyclic Compounds with Anticipated Antitumor Activity

A novel class of 5‐amino‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐1H‐pyrazole‐4‐carbohydrazides and 8‐(pyridin‐4‐yl)pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidin‐5(1H)‐ones was synthesized from reaction of 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐acetohydrazide and 7‐(pyridin‐4‐yl)‐2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐one with the appropriate hydrazonoyl halides. Moreover, 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)‐ethylidene)‐acetohydrazide was used for the synthesis of 2‐cyano‐N′‐(1‐(pyridin‐4‐yl)ethylidene)‐acrylohydrazides and 2‐oxo‐2‐(2‐(1‐(pyridin‐4‐yl)ethylidene)‐hydrazinyl)‐acetohydrazonoyl cyanides. The structures of the newly prepared compounds were confirmed by both elemental and spectral analyses as well as by alternate synthesis. The anticancer activities of the prepared compounds were screened against the hepatocellular carcinoma (HepG2) cell line, and the results showed that most of the compounds exhibit considerable activities.     

Direct introduction of heterocyclic residues into 1,2,4-triazin-5(2H)ones

3-Aryl-1,2,4-triazin-5(2H)-ones 1a-c react with indoles 2a-c in trifluoroacetic acid/chloroform or in boiling butanol or acetic acid to give 3-aryl-6-(indolyl-3)-1,6-dihydro-1,2,4-triazin-5(2H)-ones 3a-g . Oxidation of the dihydro-1,2,4-triazin-5(2H)-ones 3a-e afforded 6-(indolyl-3)-1,2,4-triazin-5(2H)-ones 4a-e , products of nucleophilic substitution of hydrogen in 1a-c . Refluxing 1b with N-methylpyrrote 5b in butanol for an extended time resulted in the formation of 3-(4-chlorophenyl)-6-(1-meuiylpyrrolyl-2)-1,2,4-triazin-5(2H)-one 4h. The reaction of 1a-c with indoles 2a-c , pyrroles 5a,b , 1,3-dimethyl-2-phenylpyrazol-4-one (8) and aminothiazoles 9a,b in acetic anhydride affords the 1-acetyl-3-aryl-6-hetaryl-1,6-dihydro-1,2,4-triazin-5(2H)-ones 6a-s . Reaction of 1a-c with N-methyl-pyrrole 5b in acetic anhydride gives beside the 1:1 addition products 6h-k also the 2:1 addition products 7a-c .     

Synthesis of Some New 1,2,3,4‐Tetrahydropyrimidine‐2‐thione and Their Thiazolo[3,2‐a]pyrimidine,Thiazino and Benzothiazepine Derivatives

The starting N‐(2‐pyridyl)‐6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxamide ( 4 ) was used as a key intermediate for the synthesis of new 1,2,3,4‐tetrahydropyrimidine‐2‐thione and their thiazolo[3,2‐a]pyrimidine, thiazino and benzothiazipen derivatives. The reaction of 4 with haloketones in ethanol catalyzed by base afforded the corresponding thiophenopyrimidine and pyrimidothiazipine derivatives 5 , 6 , 7 , 8 , 9 , 10 . Methylation and formylation of 4 led to the pyrimidine derivatives 15 and 16 , respectively. The preventative compounds were established on the basis of elemental and spectral data.