Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.     

Five-membered 2,3-dioxoheterocycles: LVIII. Reaction of methyl 1-Aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrol-2-carboxylates with substituted 1-methyl-3,4-dihydroisoquinolines. New approach to the synthesis of steroid 13-azaanalogs

Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with substituted 1-methyl-3,4-dihydroisoquinolines with the formation of substituted 3-oxo-2,3,5,6-tetra-hydropyrrolo[2,1-a]-isoquinoline-2-spiro-2′-(1-aryl-3-aroyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrroles). A new approach was developed to the synthesis of 13-azagonanes, substituted benzo[f]pyrrolo[2,1-a]isoquinoline-9-spiro-2′-pyrroles.     

Synthesis of derivatives of pyrido[3′,2′:4,5]furo[3,2-c]isoquinoline heterocyclic system

An approach to the synthesis of derivatives of new heterocyclic system, pyrido[3′,2′:4,5]-furo[3,2-c]isoquinoline, was suggested. A condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with methyl 2-(chloromethyl)benzoate and subsequent treatment of the condensation product with potassium tert-butoxide leads to substituted pyrido[3′,2′:4,5]furo[3,2-c]-isoquinolin-5(6H)-ones. Similarly, a condensation reaction of substituted 3-cyanopyridin-2(1H)-ones with 2-(chloromethyl)benzonitrile and subsequent treatment of the condensation product with potassium tert-butoxide gives substituted 5-aminopyrido[3′,2′:4,5]furo[3,2-c]-isoquinolines.     

Synthesis of functional derivatives of isothiazole and isoxazole basing on (5-arylizoxazol-3-yl)- and (4,5-dichloroisothiazol-3-yl)arylmethanol

From (4,5-dichloroisothiazol-3-yl)phenylmethanol by Ritter reaction a substituted acetamide was synthesized that at hydrolysis with HCl afforded (4,5-dichloroisothiazol-3-yl)phenylmethylamine hydrochloride. By reaction of (5-arylisoxazol-3-yl)- and 4,5-dichloroisothiazol-3-yl)arylmethanol with thionyl chloride the corresponding (1,2-azol-3-yl)arylchloromethanes were obtained. At treatment with O- and N-nucleophiles chlorine atom in chloromethylеne fragment of obtained compounds was substituted by residues of benzylamine, morpholine, vanillin, and ethoxy group.     

Synthesis of substituted thiazolo[4,5-b]pyridines and other annulated heterocycles via SN2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions

A new combinatorial method for the preparation of substituted thiazolo[4,5-b]pyridines, which utilizes cyanoacetamide, heterocumulenes (isothiocyanates, carbon bisulfide), and ethyl-4-chloroacetoacetate in a new S_N2→Thorpe-Ziegler→Thorpe-Guareschi domino reactions has been developed. The obtained thiazolo[4,5-b]pyridines were then used together with aldehydes and malononitrile in another Knoevenagel reaction→Michael reaction→hetero-Thorpe-Ziegler domino reaction for the synthesis of substituted 4,6-dihydro-5H-pyrano[2,3-d]thiazolo[4,5-b]pyridines.     

Synthesis and characterization of liquid crystalline unsymmetrically substituted phthalocyanines

The synthesis of unsymmetrically substituted phthalocyanines bearing two p-tolyl-sulfonyl (tosyl)amido and six alkylthio moieties was achieved by cyclotetramerisation of two different phthalonitrile derivatives, namely 1,2-di(alkylthio)-4,5-dicyanobenzene and 4,5-dicyano-N,N′-ditosyl-o-phenylenediamine in the presence of an anhydrous metal salt and strong base. The new compounds were characterized by elemental analyses, UV/Vis, IR, NMR and mass spectra. The mesogenic properties of these new materials were studied by differential scanning calorimetry (DSC) and polarizing optical microscopy. The mesogenic properties of these compounds were compared to that of their symmetric analogous, octaalkythia substituted phthalocyanine derivatives.     

Synthesis and properties of 1,2-dihydropyridazino[4,5-b]indole II

The possibility of the synthesis of substituted 1,2-dihydropyridazino[4,5-b]indoles by the reaction of 1-methyl-2-carbomethoxy-3-(α-halobenzyl)indole or 1-methyl-2-carbomethoxy-3-(α-acetoxybenzyl)indole with hydrazines was demonstrated. The oxidation, reduction, and acylation reactions of the resulting 1,2-dihydropyridazino[4,5-b]indoles were studied.     

Synthesis of dihydrofurans containing trifluoromethyl ketone and heterocycles by radical cyclization of fluorinated 1,3-dicarbonyl compounds with 2-thienyl and 2-furyl substituted alkenes

Manganese(III) acetate based radical cyclization of various fluorinated 1,3-dicarbonyl compounds with 2-thienyl and 2-furyl substituted alkenes produced 3-trifluoroacetyl and 2-trifluoromethyl-dihydrofurans in good yields. The radical cyclizations of 2-methyl-5-[(E)-2-phenylvinyl]furan 2b and 2-[(E)-2-phenylvinyl]thiophene 2c led to the formations of 5-(5-methyl-2-furyl)-4,5-dihydrofuran and 5-(2-thienyl)-4,5-dihydrofuran, respectively. In the reactions of 1,3-dicarbonyls with alkenes, 2-thienyl substituted alkenes formed 4,5-dihydrofurans in higher yields than 2-furyl substituted alkenes.     

Conversion of γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones

Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. This paper describes the development of a method for the direct conversion of unsubstituted and 4-substituted γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones and 2-phenyl-4,5-dihydro-2H-pyridazin-3-ones.     

Novel methods to functionalize thiazolo[4,5-c]pyridines

Novel substituted thiazole[4,5-c]pyridines have been synthesized in good yields from unsubstituted thiazole[4,5-c]pyridine using direct C-H coupling reactions and N-oxide rearrangement chemistry.     

Efficient route to benzo[4,5]imidazo[2,1-a]phthalazines

Benzo[4,5]imidazo[2,1-a]phthalazines have been obtained from various o-nitrophenylhydrazines through different 2-(2-nitrophenyl)-1,2-dihydro-1-phthalazinones as intermediates using an elaborated advanced procedure. An activated chlorine atom in 2-nitrophenyl moiety of the latter is able to undergo nucleophilic substitution for secondary alicyclic amines yielding novel substituted phthalazinones. Their one-pot reduction and cyclodehydration yield a series of novel substituted benzo[4,5]imidazo[2,1-a]phthalazines.     

Synthesis of pyrazolo[3,4-d]-4,5-dihydropyrimidin-6-ones

A small library of hitherto unprepared pyrazolo[3,4-d]-4,5-dihydropyrimidin-6-ones was synthesized on a preparative scale. The synthesis starts with a substituted 5-aminopyrazole that reacts with an isocyanate to give the corresponding urea. The latter undergoes a chlorotrimethylsilane-promoted [5+1] cyclocondensation with an aldehyde yielding the title pyrazolo[3,4-d]-4,5-dihydropyrimidin-6-one. Both synthetic steps are high-yielding (74–94%). The intermediates and the target compounds were isolated by simple crystallization. Ketones with the exception of isatin do not react with the open-chain urea intermediates.     

Three-component condensation of 5-aminoimidazole derivatives with aldehydes and Meldrum’s acid. Synthesis of 3,4,6,7-tetrahydroimidazo[4,5-b]pyridin-5-ones

A convenient method for the synthesis of the earlier unknown substituted 3,4,6,7-tetrahydroimidazo[4,5-b]pyridin-5-ones was developed based on a three-component condensation of 5-aminoimidazole derivatives, aldehydes, and Meldrum’s acid. Unstable aminoimidazole derivatives were readily formed in situ by decarboxylation of 5-amino-4-imidazolecarboxylic acids in acidic medium at room temperature, whose sodium salts were obtained by the alkaline hydrolysis of the corresponding, readily available esters.     

Ring-opening and recyclization of 3,4-diacylfuroxans by nitrogen nucleophiles

Interaction of 3,4-diacylfuroxans with hydroxylamine hydrochloride results in the formation of substituted 4,5-bis (hydroximino)-4,5-dihydroisoxazoles, whereas the reaction of 3,4-bis(4-methylfurazanoyl-3)furoxan with hydrazine hydrate in acetic acid affords 3-[4,5-bis(hydroximino)-4,5-dihydro-1H-pyrazol-3-yl]-4-methylfurazan. N-Acyl-, N-nitro-, N-alkyl- and N-adamantyl derivatives of the latter compound have been synthesized. X-Ray structure determinations together with density functional theoretical calculations are reported.     

A new approach to the synthesis of 4-(N-aryl)carbamoylmethyl-4,5-dihydropyridazin-3(2H)-ones

Reaction of N-aryl substituted maleimides with aliphatic ketazines leads to the formation of 4,5-dihydropyridazin-3(2H)-ones in moderate yields. The reaction proceeds through 1,4-addition of an azine to the maleimide double bond, as confirmed by separation of the corresponding adducts in some cases, which are then converted into 4,5-dihydropyridazin-3(2H)-ones. In addition, the solid-state synthesis of 4,5-dihydropyridazin-3(2H)-ones is demonstrated for the first time.     

Skeletal Wagner-Meerwein rearrangement of perhydro-3a,6;4,5-diepoxyisoindoles

An investigation of a skeletal Wagner-Meerwein rearrangement of variously substituted or quinoline-annulated 3a,6;4,5-diepoxyisoindol-1-ones is reported. Optimum reaction conditions (Ac₂O, BF₃·OEt₂, rt) were discovered for the formation of the target 4,6-epoxycyclopenta[c]pyridines in 40-80% yields. It was shown that the direction of the sigmatropic rearrangement of 3a,6;4,5-diepoxyisoindol-1-ones depended dramatically on the carboxyl group position (exo-/endo-) in the oxabicyclo[2.2.1]heptane moiety. The spatial structure of previously unknown 7,9-epoxycyclopenta[4,5]pyrido[1,2-a]quinolines derived from Wagner-Meerwein rearrangement of 2,11b-epoxyoxireno[6,7]isoindolo[2,1-a]quinolines was established based on the X-ray analysis data. The skeletal rearrangement proceeded regio- and stereospecifically in all the cases examined due to the absence of the epimerization of the carbon atoms adjacent to the carbocation centres.     

The synthesis and characterisation of N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides and related pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-ones as potential enantioselective organocatalysts

The acylation of substituted 2-aminopropanamides with (2S)-Boc-proline, (2S)-Cbz-proline and (2S)-Bn-proline was used to prepare substituted 1-protected N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides (74-89%), whose subsequent deprotection gave N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides (94-95%). The enantiomerically pure N-(1-carbamoyl-1,1-dialkyl-methyl)-(S)-prolinamides obtained were tested as organocatalysts for the aldol reaction of cyclohexanone with 4-nitrobenzaldehyde, with yields ranging from 38% to 79% ee. The highest enantioselectivity (89% ee) was achieved by catalysis with N-(1-carbamoyl-cyclopentyl)-(S)-prolinamide (methanol, l0% HCl). By the action of sodium methoxide, Boc-N-(1-carbamoyl-cyclopentyl)-(S)-prolinamide was quantitatively cyclised to 2-(1-Boc-pyrrolidin-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one, which was accompanied by racemisation at the stereogenic centre of the proline skeleton. Alternatively, the substituted 4,4-dialkyl-2-pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-ones were prepared by oxidation of 4,4-dialkyl-2-((2S)-1-Boc-pyrrolidin-2-yl)-4,5-dihydro-1H-imidazolidin-5-ones (54-69%). In an acid medium, 2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one and (4S)-4-isopropyl-4-methyl-2-pyrrolidin-2-yl-4,5-dihydro-1H-imidazol-5-one underwent racemisation. Conversely, the free base of (2S)-2-pyrrolidin-2-yl-1,3-diazaspiro[4.4]non-1-en-4-one very easily underwent oxidation to give the achiral 2-(4,5-dihydro-3H-pyrrol-2-yl)-1,3-diazaspiro[4.4]non-1-en-4-one.     

Regioselective synthesis of 5,6-polymethylene-3-cyanopyridine-2(1H)-thiones and fused heterocycles based on them

Condensation of 2-hydroxymethylenecyclopentan-1-one or -cyclooctan-1-one sodium salts with cyanothioacetamide afforded 5,6-polymethylene-3-cyanopyridine-2(1H)-thiones which were regioselectively alkylated at the sulfur atom by alkyl halides. Derivatives of 3-cyanopyridine-2(1H)-thione and 2-alkylthio-3-cyanopyridine were used for regioselective synthesis of substituted heterocycles: 3-aminothieno[2,3-b]pyridines, pyrido[2,3∶2′,3′]thieno[4,5-d]pyrimidines, and pyrido[2,3∶2′,3′]thieno[4,5-d]oxazines.     

Synthesis of New Amides of Isoxazole- and Isothiazole-Substituted Carboxylic Acids Containing an Arylaminopyrimidine Fragment

By acylation of substituted 2-aminoarylpyrimidines with 5-phenyl(p-tolyl)isoxazole- and 4,5-dichloroisothiazole-3-carbonyl chlorides new amides of pyrimidine series were obtained.     

Reaction of 1-alkyl(aryl)-5-alkyl(aryl)amino-2-oxo-2,3-dihydro-H-imidazole-4-carbonitriles with Lawesson’s reagent

The reaction of substituted 2-oxo-2,3-dihydro-1H-imidazole-4-carbonitriles with Lawesson??s reagent gave new compounds of the fused imidazo[4,5-d][1,3,2]diazaphosphinine system.