New Synthesis of Pyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>]pyridines

A new efficient method has been developed for the synthesis of highly biologically active pyrano-[4,3-d]pyrazolo[3,4-b]pyridines on the basis of Smiles rearrangement of ethyl [(8-alkyl(aryl)-5-cyano-3,3-dimethyl-3,4-dihydro-1H-pyrano[3,4-c]pyridin-6-yl)oxy]acetates. Intermediate acetohydrazides have also been isolated. The proposed procedure is advantageous due to the possibility of avoiding experimentally difficult chlorination stage.     

Pyrano[4,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidinium salts

Reactions of 5-aryl- and 5,7-diaryl-1,3-dimethyl-2,4-dioxopyrano[4,3-d]pyrimidinium salts with hydrazine were studied. In the former case, the reaction products were the 6-amino-1,3-dimethyl-2,4-dioxopyrido[4,3-d]pyrimidinium salts. 5,7-Diarylpyrano[4,3-d]pyrimidinium salts were transformed into either the corresponding pyridinium salts or 1H-pyrimido-[5,4-d][1,2]diazepine-2,4(3H,9H)-diones, depending on the hydrazine concentration and the reaction time. For Part 1, see Ref. 1. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1720–1725, May, 2008.     

Synthesis of novel condensed pyridines and pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

Methods have been developed for the synthesis of novel derivatives of pyrano[3,4-c]pyridines, 2,7-naphthyridines, and condensed pyrido[2,3-d]pyrimidines by condensation of thiopyranthiones.     

Ultrasound-Assisted Synthesis of 5<Emphasis Type="Italic">H</Emphasis>-Chromeno[2,3-<Emphasis Type="Italic">b</Emphasis>]pyridine Derivatives

An environmentally friendly method has been developed for the preparation of 5H-chromeno[2,3-b]pyridine derivatives in an aqueous medium under ultrasound irradiation.     

Synthesis of 2,3-disubstituted derivatives of pyrano-, thiopyrano-, and benzoannelated pyrido[2,3-<Emphasis Type="Italic">b</Emphasis>]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

A new methods have been developed for the synthesis of condensed pyrido[2,3-b]thieno[3,2-d]pyrimidines based on cyclic derivatives of 4-cyanopyridine-3-thiones. The presence of two different reactive functional groups NH₂ and CONH gives the possibility of carrying out different conversions of thieno[2,3-b]pyridines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1245–1252, August, 2008.     

Single-step synthesis of substituted 7-aminopyrano[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

A single-step method for the synthesis of substituted 7-aminopyrano[2,3-d]pyrimidines was developed. The method involves a three-component reaction of barbituric acid or 4,6-dihydroxypyrimidine with aromatic aldehydes and malononitrile in DMF in the presence of N-methylmorpholine as a catalyst.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2242–2244, October, 2004.     

Synthesis and X-ray study of 6<Emphasis Type="Italic">H</Emphasis>-chromeno[3,4-<Emphasis Type="Italic">e</Emphasis>][1,3,4]triazolo[2,3-<Emphasis Type="Italic">a</Emphasis>]pyrimidine

2-Dimethylamino methylenechromanone 1 reacted with 4H-1,2,4-triazol-3-amine in acetic acid to give only one isolated product which was identified by X-ray study as 6H-chromeno[3,4-e][1,3,4]triazolo[2,3-a]-pyrimidine. The molecular structure of 3, C₁₂H₈N₄O, was determined to be monoclinic, P2₁/c, a = 16.3875(5), b = 8.8378(3), c = 13.8392(5) Å, β = 101.190(1)°, V = 1966.22(11) ų, Z = 8.     

Synthesis of 2-hetarylimidazo[4,5-<Emphasis Type="Italic">d</Emphasis>]pyridazine derivatives

2-Chloropyridine-3,4-diamine reacted with hetarenecarboxylic acids (pyridine-2-, pyridine-3-, and pyridine-4-carboxylic acids and 6-oxo-1,6-dihydropyridazine-3-carboxylic acid) in polyphosphoric acid at 160–170°C to give the corresponding 2-hetarylimidazo[4,5-c]pyridin-4-ones. Nitration of the latter with a mixture of concentrated nitric and sulfuric acids led to the formation of 2-hetaryl-7-nitroimidazo[4,5-c]pyridin-4-ones which were converted into 2-hetaryl-7-methylimidazo[4,5-d]pyridazin-4-ones by the action of hydrazine hydrate at 140–150°C.     

Synthesis of pyrrolo[3,2-<Emphasis Type="Italic">d</Emphasis>][1,3]thiazoles

By oxidation of monothiooxamides with K₃[Fe(CN)₆]pyrrolo[3,2-d][1,3]thiazoledicarboxylic acid was obtained used further in the synthesis of 2,4,5-trimethyl-4H-pyrrolo[3,2-d][1,3]thiazole.     

Pyrazoles and Pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>]pyrrolo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrazines,I. Synthesis and Antimicrobial Activity

Summary. The synthesis of the title compounds was achieved using 1-phenyl-5-(pyrrol-1-yl)-1H-pyrazole-3-carboxylic acid azide as starting material. The latter compound was allowed to react with alcohols and amines to afford the corresponding carbamates and urea derivatives. Alkaline hydrolysis of the carbamates gave the corresponding amine, which was acylated and/or aroylated to give amide derivatives. These and the urea derivatives were subjected to cyclodehydration to give the title compounds. Antibacterial and antifungal activities were observed for several derivatives.     

Efficient and library-friendly synthesis of 4-<Emphasis Type="Italic">N</Emphasis>-substituted 6-bromopyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines under microwave irradiation

In this paper, a novel synthetic method for 4-N-substituted 6-bromopyrido[2,3-d]pyrimidines was reported. Starting from 2-aminonicotinonitrile, following by bromination of aromatic ring, condensation, cyclization, and Dimroth rearrangement, a series of 21 new pyrido[2,3-d]pyrimidine derivatives was prepared in high yields (up to 98%). In the last two steps, microwave irradiation was used. The structures of synthesized compounds were determined by NMR, IR, and HRMS techniques. The results showed that application of microwave irradiation has a beneficial effect for the preparation of desired products, as it is simple and efficient method for improving the yields and reducing the formation of undesirable by-products.     

Synthesis of alkyl thioethers of pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidine

Reaction of 4-imino-1-methyl-5-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine-6-thione with unsaturated alkyl halides gives 4-imino-6-methallylthio(cinnamylthio, allylthio)-1-methyl-5-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidines.     

Ecofriendly synthesis of substituted pyridine and pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine derivatives

An environmentally benign novel one-pot synthesis of pyridines and pyrido[2,3-d]pyrimidines from chalcones and malononitrile was described. In the reaction under neat conditions using microwave irradiation, enhancement in the reaction rate and high yields were observed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1479–1482, June, 2005.     

Reaction of trifluoroacetylchromenes with 6-aminouracils. Synthesis of pyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidines

The condensation of trifluoroacetyl-substituted 4H-chromenes and 1H-benzo[f]chromenes with 6-amino-1,3-dimethyluracil and 6-aminothiouracil afforded a number of pyrido[2,3-d]pyrimidine derivatives containing a 2-hydroxybenzyl or 2-hydroxynaphthalen-1-ylmethyl group in the 6-position as a result of cascade transformation initiated by Michael addition.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Molecular design of pyrazolo[3,4-<Emphasis Type="Italic">d</Emphasis>]pyridazines

Reactions of arenediazonium chlorides with ethyl 2-methyl-and 2-chloro-4-oxobutanoates gave, respectively, ethyl 2-(arylhydrazono)propanoates and chloro(arylhydrazono)acetates. Ethyl 2-(arylhydrazono)-propanoates reacted with the Vilsmeier-Haak reagent to give ethyl 1-aryl-4-formyl-1 H-pyrazole-3-carboxylates. Ethyl 1-aryl-4-acetyl-5-methyl-1H-pyrazole-3-carboxylates were obtained by reaction of chloro(arylhydrazono) acetates with acetylacetone. Reactions of the obtained pyrazole derivatives with hydrazine and methylhydrazine led to the formation of the corresponding 3,4-R ₂ ¹ -6-R²-2-aryl-2,6-dihydro-7H-pyrazolo-[3,4-d]pyridazin-7-ones (R¹, R² = H, Me) which were subjected to alkylation and sulfurization.     

Synthesis and functionalization of 7-hydroxyanthra[2,1-<Emphasis Type="Italic">b</Emphasis>]benzo[<Emphasis Type="Italic">d</Emphasis>]furan-8,13-diones

The diazotization of 1-amino-2-aryloxy-4-hydroxy-9,10-anthraquinones in various solvents and subsequent heating of the diazotization products lead to 7-hydroxyanthra[2,1-b]benzo[d]furan-8,13-diones. When consecutively treated with benzenesulfonyl chloride and amines, the products form 7-aminoanthra[2,1-b]benzo[d]furan-8,13-diones.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]-1,2,4-triazolo[4,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidin-5-ones

Abstract  The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species. Graphical abstract        

One-Step Three-Component Synthesis of New 2,5,6,7-Functionalized 5,8-Dihydropyrido-[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

One-step three-component cyclocondensation of 2,6-disubstituted pyrimidin-4(3H)-ones with 1,3-dicarbonyl compounds and some aromatic and heterocyclic aldehydes on heating or under microwave irradiation afforded new functionally substituted 5,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones. Conventional heating was found to be more advantageous. The effects of the 2-substituent in the initial pyrimidin-4(3H)-one and the nature of the dicarbonyl component on the product structure and yield were analyzed.