Synthesis of 2,4‐disubstituted 6‐phenyl‐7H‐pyrrolo[3,2‐d]‐pyrimidin‐7‐one 5‐oxides

A relatively short and efficient method for the utilization of 4,6‐dichloro‐2‐methylthio‐5‐nitropyrimidine ( 1 ) in the synthesis of the poly substituted pyrrolo[3,2‐d]pyrimidin‐7‐one 5‐oxides ( 6a ‐g) is reported. Some new 4‐substituted 6‐chloro‐2‐methylthio‐5‐nitropyrimidines ( 2a‐e ) were prepared by reaction of 4,6‐dichloro‐2‐methylthio‐5‐nitropyrimidine ( 1 ) with amines. 4‐Substituted 2‐methylthio‐5‐nitro‐6‐phenylethynylpyrimidines ( 3a‐e ), obtained from 4‐substituted 6‐chloro‐2‐methylthio‐5‐nitropyrimidines ( 2a‐e ) via palladium‐catalyzed Sonagashira coupling reaction with 1‐phenylacetylene, underwent smooth cyclization reaction in boiling 2‐propanol in the presence of catalytic amount of pyridine to give 4‐substituted 2‐methylthio‐6‐phenyl‐7H‐pyrrolo[3,2‐d]pyrimidin‐7‐one 5‐oxides ( 4a‐e ). The methylthio group of the latter compounds can be easily and selectively oxidized by m‐chloroperbenzoic acid and replaced with different amines.     

The gould‐jacob type of reaction for the synthesis of novel pyrimidopyrrolopyrimidines: A comparison of classical heating vs solvent free microwave irradiation

The Gould‐Jacob type of reaction for the synthesis of ethyl 4‐oxo‐8,10‐substituted‐4,8‐dihydropyrimido[1,2‐c]pyrrolo[3,2‐e]pyrimidine‐3‐carboxylates 5 has been carried out conventionally by the condensation between 4‐aminopyrrolo[2,3‐d]pyrimidines 2 and diethyl ethoxymethylenemalonate 3 via acyclic intermediates diethyl N‐[5,7‐substituted‐7H‐pyrrolo[2,3‐d]pyrimidin‐4‐yl]aminomethylenemalonates 4 and the results obtained were compared with single step microwave irradiation under solvent free conditions for the synthesis of 5 .     

Regioselective synthesis of novel spiroheterocyclic framework via the 1,3‐dipolar cycloaddition

A series of novel dispiro[oxindole‐fused pyrimidine]pyrrolidine ring systems 4a‐f were synthesized by the regioselective 1,3‐dipolar cycloaddition reaction of the 2‐arylmethylene‐7‐benzyl‐9‐(benzylidene)tetrahydropyrido[4,3‐d]thiazolo[3,2‐a]pyrimidin‐3‐ones 1a‐f with azomethine ylides, generating by the decarboxylative route from isatin 2 and sarcosine 3 , in moderate to good yields. The regiochemistry of designed dispiroheterocyclic compounds 4a‐f was established by single crystal X‐ray structure and spectroscopic techniques.     

Preparation of 5‐methyl‐2‐sulfanyl‐7h‐1,3,4‐thiadiazolo[3,2‐a]‐pyrimidin‐7‐ones

7H‐1,3,4‐Thiadiazolo[3,2‐a]pyrimidin‐7‐ones can be prepared by the acylation of 5‐amino‐1,3,4‐thiadiazoles with diketene and subsequent ring closure (dehydration). Whereas arylthio substituents (SC₆H₅) can be introduced in 2‐position by the replacement of Br, alkylthio groups (SC₂H₅) have to be already presentin the starting 5‐amino‐1,3,4‐thiadiazole. The ambident nucleophile 2‐thiazolidinethione reacts in the Br substitution reaction on the N atom.     

A facile synthesis of 2‐substituted thieno[3′,2′‐5,6]‐pyrido[4,3‐d]pyrimidin‐4(3H)‐ones

The thienopyridine derivative 2 , obtained from reaction of acetoacetic ester with 1 in the presence of tin tetrachloride, was treated with triphenylphosphine in hexachloroethane and Et₃N to give iminophosphorane 3 . Iminophosphorane 3 reacted with phenyl isocyanate to give carbodiimide 4 , which was further treated with phenols or ethenol to produce 2‐substituted 5,8,9‐trimethyl‐3‐phenyl‐thieno[3′,2′‐5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 5 in presence of catalytic amount of K₂CO₃ or EtONa. The structures of compounds 5 were confirmed by ¹H NMR, IR, MS, and elemental analysis.     

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 of 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones and their reactions with nucleophiles

[2‐Alkylthio‐6‐methyl‐4‐oxopyrimidin‐3(4H)‐yl]acetonitriles ( 3‐5 ) treated with sodium methoxide in methanol followed by ammonium chloride were cyclized to 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones ( 6‐8 ). Under acid or base‐catalyzed hydrolysis they were converted to 7‐methyl‐imidazo[1,2‐a]pyrimidine‐2,5‐[1H,3H]‐diones ( 9‐11 ), whereas in the reaction with butyl‐ or benzylamine the corresponding 7‐methyl‐2‐(substitutedamino)imidazo[1,2‐a]pyrimidin‐5(3H)‐ones ( 13‐18 ) were produced. The latter were found to exist in two tautomeric forms in CDCl₃ solution.     

Synthetic studies connected with the preparation of h+/k+‐ATPase inhibitors rabeprazole and lansoprazole

Synthesis of lansoprazole and rabeprazole using common intermediates is devised. The common intermediates, 2‐[(4‐nitro‐3‐methylpyridin‐2‐yl)methanesulfanyl]‐1H‐benzoimidazole and 2‐[(4‐chloro‐3‐methyl‐pyridin‐2‐yl)methanesulfanyl]‐1H‐benzoimidazole, were prepared in several ways.     

New access to thiazolo[4,5‐d]pyrimidine derivativess

4‐Amino‐5‐bromo‐2‐substituted‐aminopyrimidines are readily obtained from the newly prepared 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by sequential treatment with ethanolic ammonia and secondary amines. These compounds were successfully reacted with various isothiocyanates in the presence of sodamide in DMF to form the new thiazolo[4,5‐d] pyrimidine derivatives.     

Synthesis and intramolecular cyclization of 2‐methylsulfany‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide

Treatment of ambident sodium salt of 2‐methylsulfanyl‐4(3H)‐quinazolinone with methyl bromoacetate resulted in N₍₃₎‐alkyl ester formation. Reaction of the resulted ester with hydrazine hydrate gave 2‐methylsulfanyl‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide, which underwent intramolecular cyclization under heating in dimethylformamide to give 1‐aminoimidazo[2,1‐b]quinazoline‐2,5(1H,3H)‐dione. The latter took place in acylation reaction and in condensation with aromatic aldehydes.     

Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds

A number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9 , which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by ¹H and ¹³C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.     

Synthesis of 2‐amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐4H‐5,6,7,8‐tetrahydrobenzo[b]pyran derivatives in ionic liquid medium

In this paper, preparation of 2‐Amino‐4‐aryl‐7,7‐dimethyl‐5‐oxo‐4H‐5,6,7,8‐tetrahydrobenzo[b]pyran derivatives from aromatic aldehyde, malononitrile or cyanoacetate and 5,5‐dimethyl‐1,3‐cyclohexanedione in ionic liquid [bmim⁺][BF₄^?] was described. Compared with other methods, this new method has the advantages of easier work‐up, milder reaction conditions, high yields and environmentally benign procedure.     

Ready access to 7,8‐dihydro‐ and 1,2,3,4‐tetrahydro‐1,6‐naphthyridine‐5(6H)‐ones from simple pyridine precursors

Short pathways are described for the synthesis of a representative example of each of the 7,8‐dihydro‐and 1,2,3,4‐tetrahydro‐1,6‐naphthyridine‐5(6H)‐one ring systems from simple pyridine precursors. An attempted synthesis of the related 4,6‐dihydro‐1,6‐naphthyridin‐5(1H)‐one ring system from a common intermediate was unsuccessful.     

An efficient one‐pot synthesis of 6‐aryl‐5‐cyano‐2‐thiopyrimidinone derivatives and their piperidinium ionic forms,x‐ray crystal structures

Three‐component condensation of benzaldehyde derivatives, alkyl cyanoacetates and thiourea in the presence of piperidine in reflux condition provides a direct route to piperidinium 6‐aryl‐5‐cyano 2‐thiopyrimidonate salts in good yields. These reactions were also carried out under microwave irradiation. The yields of products under the microwave condition were better as compared to the reflux media. The acidification of these ionic forms resulted in the formation of 6‐aryl‐5‐cyano‐2‐thiopyrimidone derivatives. The X‐ray structures of the ionic forms ( 4, 5 , and 7 ) show that there are anionic thiopyrimidinone skeletons hydrogen bridged with piperidinium cations.     

Regioselective synthesis of heterocyclic scaffold by aryl radical cyclization

Regioselective synthesis of a number of coumarin‐annulated pentacyclic heterocycles have been achieved by tri‐n‐butyltin hydride‐mediated aryl radical cyclization. The products are formed as a mixture of cis‐ and trans‐ forms which were successfully separated by careful silica gel flash chromatography.     

Novel regioselective synthesis of 3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐one containing compounds

A variety of 3″,5″‐diaryl‐3″H,4′H‐dispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]thiadiazol]‐4′‐ones 3a‐c were synthesized regioselectively through the reaction of 4′H,5H‐trispiro[cyclohexane‐1,2′‐chromene‐3′,2″‐[1,3,4]oxadithiino[5,6‐c]chromene‐5″,1″′‐cyclohexan]‐4′‐one ( 1 ) with nitrilimines (generated in situ via triethylamine dehydrohalogenation of the corresponding hydrazonoyl chlorides 2a‐c ) in refluxing dry toluene. Single crystal X‐ray diffraction studies of 3a,b add support for the established structure. Similarly, 3′,5′‐diaryl‐2,2‐dimethyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5a‐c were obtained in a regioselective manner through the reaction of 2,2,5′,5′‐tetramethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino[5,6‐c]chromen]‐4‐one ( 4a ) with nitrilimines under similar reaction conditions. On the other hand, reaction of 2,5′‐diethyl‐2,5′‐dimethyl‐4H,5′H‐spiro[chromene‐3,2′‐[1,3,4]oxadithiino‐[5,6‐c]chromen]‐4‐one ( 4b ) with nitrilimines in refluxing dry toluene afforded the corresponding 3′,5′‐diaryl‐2‐ethyl‐2‐methyl‐3′H,4H‐spiro[chromene‐3,2′‐[1,3,4]thiadiazol]‐4‐ones 5d‐f as two unisolable diastereoisomeric forms.     

The synthesis of new azoniathiahelicenes

Synthesis of new azonia derivatives of thia[6]helicene ( 1 ) and thia[7]helicene ( 2 ) is described. The Knoevenagel condensation of 2‐methylbenzothieno[3,2‐a]quinolizinium salt ( 8 ) with appropriate arylaldehydes yielded 2‐(arylvinyl)benzothieno[3,2‐a]quinolizinium salts ( 9 and 10 ), respectively. Photocyclization of 2‐styrylbenzothieno[3,2‐a]quinolizinium salt ( 8 ) gave 7a‐azonia‐5‐thia[6]helicene ( 1 ) in 63% yield. Similarly, 2‐[2‐(2‐naphthyl)vinyl]benzothieno[3,2‐a]quinolizinium salt ( 10 ) afforded 7a‐azonia‐5‐thia[7]helicene ( 2 ) in 56% yield. The complete and unambiguous assignment of their ¹H‐ and ¹³C‐nmr spectra was performed by utilizing two‐dimensional nmr spectroscopic methods.     

Synthesis of some new 4‐substituted‐3, 5‐bis(2‐pyridyl)‐1h‐pyrazole

Several 4‐substituted‐3, 5‐bis(2‐pyridyl)‐1H‐pyrazoles, where the substituent is chloro, bromo, iodo, nitro, diazo, were synthesized under mild reaction conditions in high yields. The structures of the products were characterized by ¹H NMR, ¹³C NMR, ESI‐MS, IR and elemental analyses.     

Some nucleophilic substitutions in 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine

In some nucleophilic substitution reactions of 2‐cyano‐3‐nitroimidazo[1,2‐a]pyridine, nitrogen (alkylamines, guanidine) and oxygen nucleophiles (alkoxides) underwent substitution of the 2‐cyano group, while sulfur nucleophiles (alkylthiols) underwent substitution of the 3‐nitro group.     

Synthesis and characterization of 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles

The synthesis of a new set of selenadiazoles, 4‐aryl‐5‐(1‐aryl‐2‐methyl‐2‐nitropropyl)‐1,2,3‐selenadiazoles ( 4 ) derived from 2‐[4‐methyl‐4‐nitro‐1,3‐diarylpentylidene]‐1‐hydrazinecarboxamide ( 3 ) has been reported. THF has been found to be the solvent of choice for this reaction. Structural features of 3 and 4 have been analyzed by NMR and X‐ray techniques.