Synthesis and Structure of 2‐Substituted Thieno[3′,2′:5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one Derivatives

A series of new 2‐substituted 3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐ones 8 were synthesized via an aza‐Wittig reaction. Phosphoranylideneamino derivatives 6a or 6b reacted with 4‐chlorophenyl isocyanate to give carbodiimide derivatives 7a or 7b , respectively, which were further treated with amines or phenols to give compounds 8 in the presence of a catalytic amount of EtONa or K₂CO₃. The structure of 2‐(4‐chlorophenoxy)‐3‐(4‐chlorophenyl)‐5,8,9‐trimethylthieno[3′,2′: 5,6]pyrido[4,3‐d]pyrimidin‐4(3H)‐one ( 8j ) was comfirmed by X‐ray analysis.     

Efficient Synthesis of New Thieno[2,3‐d]pyrimidin‐4(3H)‐one Derivatives for Evaluation as Anticancer Agents

Thieno[2,3‐d]pyrimidinones were reported to act as potent anticancer agents; in this work, a series of new substituted thieno[2,3‐d]pyrimidinone ( 6 ) were synthesized via the aza‐Wittig reaction in satisfactory yields. The structures of these compounds were confirmed by elemental analysis, IR, ¹H‐NMR, and mass spectral data, and compound 6h was further analyzed by single crystal X‐ray diffraction. Cytotoxic effect of all the compounds was carried out on human breast and lung cancer cell lines (MCF‐7 and SPC‐A‐1, A459). Compound 6f exhibited the best inhibition activities against A459 with IC₅₀ 4.1 μM.     

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 of Furo[2,3‐d]pyridazin‐4(5H)‐one and Its N(5)‐Substituted Derivatives

We report the efficient preparation of furo[2,3‐d]pyridazin‐4(5H)‐one and its N‐substituted derivatives starting from methyl 2‐methylfuran‐3‐carboxylate. The Me group was converted to the aldehyde group, which was then condensed with hydrazine derivatives. Then, the ester functionalities were hydrolyzed to the corresponding acids, followed by treatment with SOCl₂ to give N‐substituted furopyridazinone derivatives.     

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.     

An Efficient Synthesis of 3H‐Pyrrolo[3,2‐d]pyrimidin‐4(5H)‐one Derivatives via an Iminophosphorane

The iminophosphorane ( 3 ), obtained from reaction of ethyl 3‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrrole‐2‐carboxylate ( 2 ) with triphenylphosphine, hexachloroethane, and triethylamine, reacted with aromatic isocyanates to give carbodiimides ( 4 ). Further reaction of 4 with various amines, phenols, or ROH to give 2,3,5,7‐tetrasubstituted 3H‐pyrrolo[3,2‐d]pyrimidine‐4(5H)‐ones ( 6 ) in satisfactory yields in the presence of catalytic amount of sodium alkoxide or solid potassium carbonate.     

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.     

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.     

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     

1‐(4,6‐Diethoxy­pyrimidin‐2‐yl)‐2‐thioxo‐2,3‐dihydro­pyrido[2,3‐d]pyrimidin‐4(1H)‐one

In the title compound, C₁₅H₁₅N₅O₃S, two parallel inter­molecular N—H⋯S hydrogen bonds, forming an eight‐membered ring, link two mol­ecules into a dimer unit; these dimer units linked into a chain of edge‐fused rings by weak C—H⋯O hydrogen bonds.     

A Facile Synthesis of 2‐Substituted 2,3‐Dihydro‐4(1H)‐Azuleno[2,1‐d]Pyrimidinones

A facile, efficient, and novel approach to access 2‐substituted 2,3‐dihydro‐4(1H)‐azuleno[2,1‐d]pyrimidinones was developed by condensation of 2‐amino‐1‐carbamoyl‐3‐phenylazulene with ary1 aldehydes or ketones in ionic liquids by catalyzed p‐toluenesulfonic acid.     

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.     

Bis(enaminones) as Versatile Precursors for Novel Bis([1,2,4]triazolo[1,5‐a]pyrimidines) and Bis(2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones)

Novel bis([1,2,4]triazolo[1,5‐a]pyrimidines) and bis(2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones) were prepared utilizing bis(enaminones) as precursors. The structures of the prepared compounds were elucidated by several spectral tools as well as elemental analyses.     

[DBU‐H]+ and H2o as effective catalyst form for 2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones: A DFT Study

DFT investigations are carried out to explore the effective catalyst forms of DBU and H₂O and the mechanism for the formation of 2,3‐dihydropyrido[2,3‐d]‐pyrimidin‐4(1H)‐ones. Three main pathways are disclosed under unassisted, water‐catalyzed, DBU and water cocatalyzed conditions, which involves concerted nucleophilic addition and H‐transfer, concerted intramolecular cyclization and H‐transfer, and Dimroth rearrangement to form the product. The results indicated that the DBU and water cocatalyzed pathway is the most favored one as compared to the rest two pathways. The water donates one H to DBU and accepts H from 2‐amino‐nicotinonitrile ( 1 ), forming [DBU‐H]⁺‐H₂O as effective catalyst form in the proton migration transition state rather than [DBU‐H]⁺‐OH^?. The hydrogen bond between [DBU‐H]⁺···H₂O··· 1 ^? decreases the activation barrier of the rate‐determining step. Our calculated results open a new insight for the green catalyst model of DBU‐H₂O. © 2015 Wiley Periodicals, Inc.     

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.     

Pyridopyrimidines. X. Synthesis of 3‐Substituted 2‐Thioxo‐5,7‐dimethylpyrido[2,3‐d] pyrimidin‐4(3H)‐ones and their S‐Alkylation Under Phase Transfer Conditions

2‐Thioxo‐5,7‐dimethylpyrido[2,3‐d]pyrimidin‐4(3H)‐ones 3 were synthesized by the cyclocondensation of 2‐amino‐3‐carbethoxy‐4,6‐dimethylpyridine 1 with methyl‐N‐aryldithiocarbamates 2 and compared with the condensation between 1 and aryl isothiocyanates 4. When a comparative study of N vs S alkylation of ambident 2‐thioxo‐5,7‐dimethylpyrido[2,3‐d]pyrimidin‐4(3H)‐ones 3 was carried out under liquid‐liquid and solid‐liquid phase transfer conditions using various alkylating agents 5 , the S‐alkylated products 6 were obtained exclusively and selectively.