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).     

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 .     

Microwave‐assisted synthesis of new regioisomeric 6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones

Novel 11‐amino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e] pyrimido[4,5‐b][1,4]diazepin‐5(5aH)‐ones 4a‐f were prepared regioselectively by the tricomponent reaction of 4,5,6‐triaminopyrimidine 1, 1,3‐indandione 2 and aromatic aldehydes 3a‐f. The bicomponent approach, using 2,4,5,6‐tetraaminopyrimidine 5 and 2‐aryl‐ideneindandiones 6a‐f as reagents, afforded 9,11‐diamino‐6‐aryl‐6,7‐dihydroindeno[1,2‐e]pyrimido[4,5‐b]‐[1,4]diazepin‐5(5aH)‐ones 7a‐f in good yields and the regioisomeric 8,10‐diamino derivatives 8a‐c in lower yields. Both, bi‐ and tricomponent approaches were performed by microwave irradiation and all products were fully characterized by detailed NMR measurements.     

An efficient synthesis of new pyrido[4′,3′:4,5]thieno[2,3‐d]‐pyrimidin‐4(3H)‐one derivatives

The carbodiimides 5 , obtained from reactions of iminophosphorane 4 with aromatic isocyanates, reacted with amines, phenols or ROH to give 2‐substituted 5,6,7,8‐tetrahydropyrido[4′,3′:4,5]thieno[2,3‐d]‐pyrimidin‐4(3H)‐one 7 in the presence of catalytic amount of sodium alkoxide or solid potassium carbonate in satisfactory yields.     

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.     

Ring closure reactions of 5‐azidopyrido[2,3‐d]pyrimidinetriones to isoxazolo‐ and oxadiazolopyrido[2,3‐d]pyrimidinetriones

Thermal decomposition of 5‐azidopyrido[2,3‐d]pyrimidines 2 and 7 having reactive ortho‐substituents such as a formyl or a nitro group yielded isoxazolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 3 or oxadiazolo‐[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 9. The reaction conditions of the azide decomposition were studied by differential scanning calorimetry (DSC). In addition, desoxygenation of N‐oxides 9 to oxadiazoles 10 and regioselective reduction of azides 7 to amines 8 were studied.     

Pyrazolo[4′,3′:5,6]pyrano[2,3‐b]quinoxalin‐4(1H)‐one: Synthesis and characterization of a novel tetracyclic ring system

Derivatives of the hitherto unknown ring system, pyrazolo[4′,3′:5,6]pyrano[2,3‐b]quinoxalin‐4(1H)‐one, are synthesized in one step from the corresponding 1‐substuituted or 1,3‐disubstituted 2‐pyrazolin‐5‐ones and 3‐chloroquinoxaline‐2‐carbonyl chloride using calcium hydroxide in boiling 1,4‐dioxane. The parent system carrying no substituent in positions 1 and 3 is obtained upon treatment of the 1‐PMB (p‐methoxybenzyl) protected congener with trifluoroacetic acid. Detailed NMR spectroscopic investigations including unambiguous chemical shift assignments of all ¹H, ¹³C, and ¹⁵N resonances of the obtained tetracycles are reported.     

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 new spiro‐[isothiochromene‐3,5′‐isoxazolidin]‐4(1H)‐ones

A series of seven new 2′,3′,4′‐substituted spiro[isothiochromene‐3,5′‐isoxazolidin]‐4(1H)‐ones ( 7‐13 ) has been prepared in the reaction of benzylidene(phenyl)azane oxide ( 5 ) or benzylidene(methyl)azane oxide ( 6 ) with (3Z)‐3‐(4‐substituted‐benzylidene)‐1H‐isothio‐ chromen‐4(3H)‐one ( 1‐4 ). The reaction occurs by a 1,3‐dipolar cycloaddition mechanism that leads to the regiospecific formation of various spiroisoxazolidines ( 7‐13 ).     

Conversion of 4-amino-1H-1,5-benzodiazepine-3-carbonitrile to pyrazolo[3,4-d]pyrimidines,pyrimido[1,6-a]benzimidazole,and pyrazolo[3′,4′:4,5]pyrimido[1,6-a]benzimidazoles

The reactions of multifunctional compounds 2a, b, c, 3a, b and 4a, b which were readily obtained from 4-amino-1H-1,5-benzodiazepine-3-carbonitrile 1 with orthoesters are described, and derivatives of pyrazolo-[3,4-d]pyrimidines 5 , pyrimido[1,6-a]benzimidazole 9 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-a]benzimidazole 10 are synthesized.     

Synthesis of new derivatives of thieno[2,3‐b]pyridine fused with octyl ring

Derivatives of thiophene, thieno[2,3‐b]pyridine, thieno[5′,4′:4,5]pyrimido[3,2‐a]pyridine and thiepine fused with octyl ring have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Studies with Heterocyclic β‐Enaminoniriles: A Simple Route for the Synthesis of Polyfunctionally Substituted Thiophene,Imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene and Thieno[3,2‐d]pyrimidine Derivatives

Reaction of 3,5‐diaminothiophene‐2‐carbonitrile derivatives 3a‐c with ethoxycarbonylmethyl isothiocyanate and/or N‐[bis(methylthio)methylene]glycine ethyl ester led to formation of 7‐substituted‐8‐amino‐5‐thioxo‐6H‐imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one derivatives 6a‐c and 7‐substituted‐8‐amino‐5‐(methylthio)imidazo[1,2:1′,6′]pyrimido[5,4‐b]thiophene‐2(3H)‐one 7a‐c , respectively. Also, the synthetic potential of the β‐enaminonitrile moiety in 3a‐c has been explored; it proved to be a promising candiate for the synthesis of 1,6‐disubstituted‐2,4‐diamino‐7,8‐dihydro‐8‐oxopyrrolo[1,2‐a]thieno[2,3‐e]pyrimidine derivatives 10a‐f and pyrido[2′,3′:6,5]pyrimido[3,4‐a]benzimidazole derivatives 12a,b .     

Synthesis of novel pyrazolo[3,4‐d]pyridazine,pyrido[1,2‐a]benzimidazole,pyrimido[1,2‐a]benzimidazole and triazolo[4,3‐a]pyrimidine derivatives

4‐Acetyl‐5‐methyl‐1‐phenyl‐1H‐pyrazole reacts with dimethylformamide dimethylacetal (DMF‐DMA) to afford the corresponding (E)1‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(N,N‐dimethylamino)‐2‐propen‐1‐one. The latter product undergoes regioselective 1,3‐dipolar cycloaddition with nitrilimines and nitrile oxides to afford the novel 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl‐1‐phenylpyrazole and 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)carbonyl isoxazole derivatives, respectively. It reacts also with 1H‐benzimidazole‐2‐acetonitrile, 2‐aminobenzimidazole and 3‐amino‐1,2,4‐triazole to afford the novel pyrido[1,2‐a]benzimidazole, pyrimido[1,2‐a]benzimidazole and the triazolo[4,3‐a]pyrimidine derivatives, respectively. The reaction of 3‐aroyl‐4‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl) carbonyl‐1‐phenylpyrazole derivatives with hydrazine hydrate led to a new pyrazolo[3,4‐d]pyridazine derivatives.     

Novel Synthesis of 3‐Amino‐4‐oxo‐(2H)‐pyrazolo[3′,4′:4,5]pyrimido‐[2,1‐b]benzothiazole and its 2‐ and 3‐Substituted Derivatives

Reaction of 4H‐pyrimido[2,1‐b]benzothiazole‐2‐thiomethyl‐3‐cyano‐4‐one (1) with hydrazine hydrate/aryl hydrazine/heteryl hydrazine in the presence of anhydrous potassium carbonate and dimethyl formamide afforded 3‐amino‐4‐oxo‐(2H)/aryl/heteryl pyrazolo[3′,4′:4,5]pyrimido[2,1‐b]benzothiazoles in good yield. These pyrazole derivatives on diazotization followed by replacement with hydroxy, chloro, bromo, iodo and on reduction gave the corresponding 3‐substituted derivatives.     

Utility of 2‐[4‐(3‐oxobenzo[f]‐2H‐chromen‐2‐yl)‐1,3‐thiazol‐2‐yl]ethanenitrile in heterocyclic synthesis

Pyrazolo[4,3‐d]pyrimidines, pyrazolo[4,3‐d]triazolino[4,3‐a]pyrimidines, 3‐(2‐thiazolyl)thiophenes, thiazolo[3,2‐a]pyridine and pyrazolo[1,5‐a]pyrimidines were synthesized from 2‐[4‐(3‐oxobenzo[f]‐2H‐chromen‐2‐yl)‐1,3‐thiazol‐2‐yl]ethanenitrile. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation and alternative synthesis route whenever possible.     

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.     

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.     

New route to pyrimido[4,5‐ e][1,3,4]thiadiazine derivatives

5‐Bromo‐2‐chloro‐4‐methyl‐6‐(1‐methylhydrazino)pyrimidine is readily obtained from the recently reported 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by treatment with methylhydrazine in chloroform. Treatment of this compound with carbon disulfide and several alkyl halides gave an intermediate which was successfully converted to its corresponding 3‐(alkylsulfanyl)‐7‐chloro‐1,5‐dimethyl‐1H‐pyrimido[4,5‐e][1,3,4]thiadiazine derivatives in basic acetonitrile. The latter compounds were reacted with secondary amines in boiling ethanol to afford the related 7‐amino derivatives.     

Regioselective three‐component synthesis of novel indeno[1,2‐b]‐pyrazolo[4,3‐e]pyridines‐fused derivatives of 4‐azafluorenone alkaloid

New fused indeno[1,2‐b]pyridine derivatives have been prepared in a multicomponent reaction from benzaldehydes, indanedione and the appropriate aminoheteroaryl compound. The simple methodology permitted the syntheses of a series of indeno[1,2‐b]pyrazolo[4,3‐e]pyridines 4 from 5‐aminopyrazol 1 and modulated by the corresponding benzaldehyde 2 .     

Transformations of phenylhydrazones of 5‐acyl‐1,2,4‐triazines to pyrazolo[4,3‐e][1,2,4]triazines or 4‐cyanopyrazole

A simple and high yielding preparation of pyrazolo[4,3‐e][1,2,4]triazines and 4‐cyano‐3‐methyl‐1‐phenylpyrazole derivatives from corresponding phenylhydrazones of 5‐acyl‐1,2,4‐triazines by melt under acidic medium and by thermal heating, respectively.