Synthesis and Herbicidal Activity of Muti‐Substituted Pyrido[4,3‐d]pyrimidin‐4‐ones

A series of novel muti‐substituted pyrido[4,3‐d]pyrimidin‐4‐one derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l were designed and synthesized by the muti‐step reaction. N,S‐acetal 1 reacted with acetyl acetamide in the presence of zinc nitrate to obtain muti‐substituted pyridine 2 , which reacted with triethyl orthoformate to give 8‐cyano‐5‐methyl‐7‐methylthio‐pyrido[4,3‐d]pyrimidin‐4‐one 3 ; the target compounds 5 were obtained in good yields by the oxidation of 3 with H₂O₂ in a catalytic amount of sodium tungstate then by the substitution with various substituted phenols. Their structures were confirmed by IR, ¹H NMR, EI‐MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate herbicidal activity against dicotyledonous weed Brassica campestris L. at the concentration of 100 mg/L. For example, compounds 5a , 5f , and 5g possessed 76.0%, 62.7%, and 60.2% inhibition against B. campestris at the concentration of 100 mg/L. Moreover, 5a exhibited 58.2% inhibition against B. campestris at the concentration of 10 mg/L.     

A Convenient Synthesis and Biological Activity of Novel Pyrido[4,3‐d]pyrimidin‐4(3H)‐ones

Fifteen novel 2‐alkylamino‐3‐aryl‐8‐cyano‐5‐methyl‐7‐(methylthio)‐pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n , 6o were designed and have been successfully synthesized via tandem aza‐Wittig and annulation reactions with the corresponding iminophosphorances 4 , aryl isocyanate, and amines in good yields. Their structures were clearly verified by IR, ¹H NMR, EI‐MS spectroscopy and elemental analysis, and in the case of compound 6i , analyzed by single‐crystal X‐ray diffraction further. The preliminary results of an in vivo bioassay showed that some compounds display moderate antifungal activity.     

A Convenient Synthesis and Biological Activity of Novel Pyrido[4,3‐d]pyrimidin‐4(3H)‐ones

Fifteen novel 2‐alkylamino‐3‐aryl‐8‐cyano‐5‐methyl‐7‐(methylthio)‐pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n , 6o were designed and have been successfully synthesized via tandem aza‐Wittig and annulation reactions with the corresponding iminophosphoranes 4 , aryl isocyanate, and amines in good yields. Their structures were clearly verified by IR spectroscopy, ¹H‐NMR spectroscopy, EI‐MS, and elemental analysis, and in the case of compound 6i , further analyzed by single‐crystal X‐ray diffraction. The preliminary results of an in vivo bioassay showed that some compounds display moderate antifungal activity.     

Molecular Iodine Promoted Synthesis of New Pyrido[2,3‐d]pyrimidin‐4‐ols

A highly ef?cient synthesis of novel pyrido[2,3‐d]pyrimidin‐4‐ols was developed via an iodine‐catalyzed tandem oxidative cyclization under focused microwave irradiation. Pyrido[2,3‐d]pyrimidin‐4‐ols were obtained from easily available 2‐amino‐4‐aryl‐6‐arylnicotinamides and benzylic amines with good to excellent yields.     

Synthesis of Derivatives of Pyrido[4,3‐d]pyrimidin‐4(3H)‐one via an Iminophosphorane

A series of new, 2‐substituted 3‐aryl‐8,9,10,11‐tetrahydro‐5‐methyl[1]benzothieno[3′,2′ : 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones, compounds 5a – q , were designed and synthesized via the aza‐Wittig reaction as the key step. The iminophosphorane 1 reacted with phenyl isocyanate (or 4‐chlorophenyl isocyanate) to the carbodiimide 4 , which was cyclized to 5 upon addition of different amines, EtOH, or phenols in the presence of a catalytic amount of EtONa or K₂CO₃ (Schemes 1 and 2). The structures of compounds 5 were confirmed by IR, ¹H‐ and ¹³C‐NMR, EI‐MS, elemental analyses, and, in the case of 5l , by single‐crystal X‐ray diffraction (Figure).     

Synthesis,Anti‐Microbial,and Cytotoxic Activities Evaluation of Some New Pyrido[2,3‐d]Pyrimidines

Novel pyridine derivatives 1d and 7 , pyrido[2,3‐d]pyrimidine derivatives 2a , 2b , 2c , 2d , 3a , 3b , 3c , 3d , 4a , 4b , 4c , 4d , 5a , 5b , 5c , 5d , 6a , 6b , 6c , 6d , 8a , 8b , and 9a , 9b were synthesized and screened for their anti‐microbial and cytotoxic activities. Compounds 2b , 2c , 3b , 3c , 5b , 5c , 6b , 6c , and 7 showed excellent anti‐microbial activities against all the tested bacteria and fungi compared to the reference drugs. Furthermore, they exhibited high safety profile in cytotoxicity test except 2c and 3c . The structures of the newly synthesized compounds were confirmed by spectral data and elemental analysis.     

Synthesis and Evaluation of PDE5 Inhibitory Activity of Novel Pyrido[2＇,1＇：5,1]pyrazolo[4,3-d]pyrimidin-4-one Derivatives

Novel pyridopyrazolopyrimidinone derivatives were designed and synthesized as potential PDE5 inhibitors. The target compounds demonstrated significant inhibitory activity against human platelet PDE5, but less potent than sildenafil.     

An Efficient Synthesis of Pyrrolo[1,2‐a] or Pyrido[1,2‐a]benzo[4,5]imidazo[1,2‐c]quinazoline Derivatives in Ionic Liquids Catalyzed by Iodine

2‐(1H ‐benzo[d ]imidazol‐2‐yl)anilines reacted with haloketones including 5‐chloropentan‐2‐one and 6‐chlorohexan‐2‐one catalyzed by iodine, giving benzo[4,5]imidazo[1,2‐c ]pyrrolo[1,2‐a ]quinazoline and 6H ‐benzo[4,5]imidazo[1,2‐c ]pyrido[1,2‐a ]quinazoline derivatives, respectively. This domino‐type reaction formed two new heterocycles and three new covalent bonds in one‐pot procedure and provided a green method for the synthesis of fused pentacyclic heterocycles bearing both quinazoline and benzimidazole moieties in ionic liquids.     

New efficient approach for the synthesis of 2‐alkyl(aryl) substituted 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones

A new, efficient and easy route for the preparation of a series of 2‐alkyl(aryl) substituted 4‐oxo‐4H‐pyrido‐[1,2‐a]pyrimidines, where alkyl = CH₃; aryl = C₆H₅, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐CH₃C₆H₄, 4‐OCH₃C₆H₄, 4‐NO₂C₆H₄ in 45–80 % yield from the reaction of β‐alkoxyvinyl trichloromethyl ketones with 2‐aminopyridine under mild conditions, is then reported.     

Synthesis of 4‐fluoroalkyl‐2H‐pyrido [1, 2‐a] pyrimidin‐2‐ones from 2, 2‐dihydropolyfluoroalkanoic acids

In the presence of N, N′‐dicyclohexylcarbodiimide, 2‐aminopyridine and its derivatives (2) condensed with 2, 2‐di‐hydropolyfluoroalkanoic adds (1) to give the corresponding amides. Subsequent intramolecular Micheal addition‐elimination reactions of the fluorine‐containing amides under basic conditions gave 4‐fluoroalkyl‐2H‐pyrido[1,2‐a]pyrimidin‐2‐ones (3) in good yields.     

Synthesis of pyrazolo[1,3,2]diazaphosphinin‐4‐ones

It was found that phosphinimidic isocyanates based on 3‐, 4‐, and 5‐aminopyrazoles could undergo intramolecular heterocyclization to yield previously unknown pyrazolo[1,3,2]diazaphosphorin‐4‐ones containing an endocyclic PN double bond. It was shown that phosphinimidic isocyanate based on 4‐aminopyrazole, in which there are two positions (3 and 5) available for the cyclization, reacts exclusively at the 5‐carbon atom. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:210–215, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21005     

Regioselective C3 Alkenylation of 4 H‐pyrido[1,2‐a]pyrimidin‐4‐ones via Palladium‐Catalyzed CH Activation

A general and efficient palladium‐catalyzed direct C3 alkenylation of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones using AgOAc/O₂ as the oxidant has been developed. A variety of 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones were successfully coupled with acrylate esters, styrenes, methylvinylketone, and acrylamide in moderate to excellent yields. The reaction exhibited complete regio‐ and stereoselectivity. This transformation provides an attractive new approach to functionalize 4H‐pyrido[1,2‐a]pyrimidin‐4‐ones.     

One‐pot Combinatorial Synthesis of Benzo[4,5]imidazo‐[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one Derivatives

A series of novel fused tetracyclic benzo[4,5]imidazo[1,2‐a]thiopyrano[3,4‐d]pyrimidin‐4(3H)‐one derivatives were synthesized via the reaction of aryl aldehyde, 2H‐thiopyran‐3,5(4H,6H)‐dione, and 1H‐benzo[d]imidazol‐2‐amine in glacial acetic acid. This protocol features mild reaction conditions, high yields and short reaction time.     

Efficient New Synthesis of N‐Arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines and Their Benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine Analogues via a Microwave‐Assisted Dimroth Rearrangement

A useful and rapid access to libraries of N‐arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines ( 1 ) and their novel benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine analogues ( 2 ) was investigated for the first time. Title compounds were obtained via microwave‐accelerated condensation and Dimroth rearrangement of suitable anilines with N′‐(2‐cyanaryl)‐N,N‐dimethylformimidamides obtained by reaction of benzo[b]furane and benzo[b]thiophene precursors with N,N‐dimethylformamide dimethyl acetal. This work also demonstrates that well‐controlled parameters offer comfortable use of microwave technology and are both safe and beneficial to the environment. Some products obtained in this article exhibit interesting in vitro antiproliferative effects.     

Base‐Mediated N‐Arylation for the Synthesis of 9H‐Pyrrolo[1,2‐a]indol‐9‐ones and 10H‐Indolo[1,2‐a]indol‐10‐ones

Treatment of 2‐bromoaryl pyrrole/indol‐2‐yl ketones with cesium carbonate in DMF resulted in the formation of 9H‐pyrrolo[1,2‐a]indol‐9‐ones and 10H‐indolo[1,2‐a]indol‐10‐ones in moderate to excellent isolated yields.     

5‐Unsubstituted Pyrido[3,2,1‐jk]carbazol‐6‐ones: Syntheses,Substitution, and Cyclization Reactions

The synthesis of the 5‐unsubstituted pyrido[3,2,1‐jk]carbazol‐6‐one 4 can be achieved by the reaction of carbazole ( 1 ) and malonate derivatives, either in a three‐step synthesis via 5‐acetyl‐pyridocarbazolone 3 or in a one‐step reaction from 1 and malonic acid/phosphoryl chloride. The 5‐acetyl derivative 5 can be transformed via a tosylate intermediate to 4‐azido‐pyridocarbazolone 11 , which cyclizes by thermal decomposition to the isoxazolo‐pyrido[3,2,1‐jk]carbazolone 12 . The thermolysis conditions were investigated by DSC. Nitration of pyridocarbazolone 4 and subsequent introduction of azide leads to azido derivative 23 , which cyclizes on thermolysis to furazan‐oxide derivative 24 . Again, the thermolysis conditions were investigated by DSC. 5‐Chloro‐5‐nitro‐pyrido[3,2,1‐jk]carbazole‐4,6‐dione, obtained from 4 by subsequent nitration and chlorination, forms by exchange of both 5‐substituents 5,5‐dihydroxy‐pyridocarbazoledione 17 , which acylates phenol to give 5‐hydroxy‐5‐(p‐hydroxyphenyl)‐pyridocarbazoledione 20 . Acid‐catalyzed cyclodehydration of 20 forms a highly fused benzofuro‐pyridocarbazole 21 . Another C–C coupling at position 5 starts from 4‐chloro‐5‐nitro‐pyridocarbazolone 22 and diethyl malonate 2a , which forms the diethyl (nitrocarbazolyl)malonate 25 . With dimethyl malonate 2c , the intermediate dimethyl (nitrocarbazolyl)malonate gives on thermolysis the (nitrocarbazolyl)acetate 27 by loss of one ester group.     

A facile synthesis of novel thiazolo[4,5‐d]pyrimidin‐7‐ones

Sixteen 5‐alkylamino‐3,6‐diaryl‐2‐thioxo‐2,3,6,7‐tetrahydrothiazolo[4,5‐d]pyrimidin‐7‐ones 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m , 4n , 4o , 4p were designed and easily synthesized via a tandem aza‐Wittig reaction. The iminophosphorane 2 , obtained from reaction of 1 with triphenylphosphine, hexachloroethane and Et₃N, reacted with aromatic isocyanate to give carbodiimide 3 . carbodiimide 3 reacted with alkylamines to provide the title compounds in 45–61% isolated yields in presence of catalytic amount of ethoxide. The structures of compounds 4 were confirmed by ¹H NMR, IR, MS, and elemental analysis. J. Heterocyclic Chem., 2011.     

Efficient synthesis of 2‐substituted thieno[2,3‐d]pyrimidin‐4(3H)‐ones via an iminophosphorane

The carbodiimides 4 , obtained from reactions of iminophosphorane 3 with aromatic isocyanates, were reacted with secondary amines to give 2‐dialkylamino‐5‐ethyl‐6‐methyl‐thieno[2,3‐d]pyrimidin‐4(3H)‐ones 6 in the presence of catalytic amount of EtONa. Reactions of 4 with phenols or ROH in the presence of the catalytic amount of K2CO₃ or RONa gave 2‐aryloxy‐ or 2‐alkoxy‐5‐ethyl‐6‐methyl‐thieno[2,3‐d]pyrimidin‐4(3H)‐ones 6 in satisfactory yields. The effects of the nucleophiles on cyclization have been investigated. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:266–270, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20424     

Synthesis of Indeno[1,2‐d]pyrimidin‐5‐Ones and Their Fluorescence in Solid State

New fluorescent compounds, 2‐substituted indeno[1,2‐d]pyrimidin‐5‐ones ( 3a , 3b , 3c , 3d ) were synthesized in good yield by the reaction of 2‐[bis(methylsulfanyl)methylene]indan‐1,3‐dione ( 1 ) with the respective amidine derivatives [guanidine carbonate ( 2a ), acetamidine hydrochloride ( 2b ), S‐methylisothiourea sulfate ( 2c ), and S‐benzylisothiourea sulfate ( 2d )]. 4‐Substituted amino‐2‐aminoindeno[1,2‐d]pyrimidin‐5‐ones ( 7b , 7c , 7d ) were synthesized by a one‐pot reaction of 1 , 2a and the respective amine compounds ( 4b , 4c , 4d ) in pyridine. These fused pyrimidine derivatives showed fluorescence in the solid state.