Reactions promoted by [hydroxy(tosyloxy)iodo]benzene in pyrazino[1,2-b]isoquinolines

The hypervalent iodine reagent PhI(OH)OTs (HTIB) promoted oxidative demethylation of 1,4-hydroquinone methyl ethers to give quinones in a quantitative conversion. The efficacy of this reaction, that has been applied to simple arene compounds and to heterocyclic systems, such as 2-isopropoxycarbonyl-7,10-dimethoxy-pyrazino[1,2-b]isoquinoline-4-ones and 1,4-diones to get the corresponding 7,10-quinones (compounds 6-8), is similar to those promoted by CAN and does not require the presence of water. Instead of oxidative demethylation, HTIB promoted in 1-methoxy-pyrazino[1,2-b]isoquinoline-4-ones complex multi-step processes to give compounds 9 or 10.     

Palladium-catalyzed intramolecular arylation of pyrimidines: a novel and expedient avenue to benzannulated pyridopyrimidines

A new efficient protocol for the synthesis of benzannulated pyrido[2,3-d]- and pyrido[3,2-d]pyrimidines has been successfully accomplished via the palladium-catalyzed intramolecular arylation of C-H bond of pyrimidine moiety. The methodology has also been extended to the synthesis of pyrimido[5,4,-c]isoquinoline-2,4,6(1H,3H,5H)-trione derivatives in excellent yields.     

Pyridazines. LIX. Synthesis of c-annelated pyridazines from 3-amino-4-pyridazinecarbonitrile

The utility of the aminonitrile 1 as an educt for the preparation of several new examples of heterocyclefused pyridazines (the [1,2,4]triazolo[1′,5′:1,6]pyrimido[4,5-c]pyridazine 7 , the pyrimido[4,5-c]pyridazines 8, 10a,b , and the pyrido[2,3-c]pyridazine 11 ) is demonstrated.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Studies in anthraquinone: Preparation of 2-substituted pyrimidoanthraquinones and related fused 1,2,4-triazolo,tetrazolo and pyrazolino derivatives

This paper describes the synthesis of 2-substituted-4(3H)-oxopyrimido[4,5-a]anthraquinone, 2-substi-tuted-4-hydrazinopyrimido[4,5-a]anthraquinones, several 2-substituted-1,2,4-triazolo[4,3-c]pyrimido[4,5-a]-anthraquinones tetrazolo[4,5-c]pyrimido[4,5-a]anthraquinones and pyrazolinopyrimidoanthraquinone derivatives.     

The synthesis of pyrimido[4,5-c]pyridazines and pyrimido[5,4-c]pyridazines

The Hofmann reaction on 6-methylpyridazine-3,4-dicarboxamide (1) gave a mixture of 3-methylpyrimido[4,5-c]pyridazine-5,7-dione (2), 3-methylpyrimido[5,4-c]pyridazine-6,8-dione (3) and an acid (4) of unknown structure. The Hofmann reaction on pyridazine-3,4-dicarboxamide (9) gave a mixture of pyrimido[4,5-c]pyridazine-5,7-dione ( 10 ) and an acid ( 11 ) of unknown structure. The reaction of 3-amino-6-methylpyridazine-4-carboxamide ( 18 ) with ethyl orthoformate gave 3-methylpyrimido[4,5-c]pyridazin-5-one ( 21 ). 4-Aminopyridazine-3-carboxamide ( 36 ) upon fusion with urea gave pyrimido[5,4-c]pyridazine-6,8-dione ( 37 ) while with ethyl orthoformate 36 gave pyrimido[5,4-c]pyridazin-8-one ( 38 ). Pyrimido[5,4-c]-pyridazine-8-thione ( 39 ) was obtained by the action of phosphorus pentasulfide on 38. 4-Amino-3-cyanopyridazine ( 16 ) when treated with formamide produced 8-aminopyrimido[5,4-c]-pyridazine ( 41 ). The synthesis of 4-aminopyridazine-3-carboxamide ( 36 ) and 4-amino-3-cyanopyridazine ( 16 ), both key intermediates in the synthesis of the novel pyrimido[5,4-c]pyridazine ring system was accomplished by the Reissert reaction of 4-aminopyridazine-2-oxides and subsequent conversion of the nitrile to the amide.     

Synthesis of tetra- and pentaaza heterocyclic systems and benzimidazo[1,2-c]quinazoline derivatives

5,6-Dihydropyrimido[5′,4′: 5,6]pyrido[1,2-a]benzimidazole and pyrimido[4′,5′: 4,5]pyrimido[1,6-a]-benzimidazole derivatives were synthesized starting from 3-[4-hydroxy-6-methyl(hydroxy)-2-phenylpyrimidin-5-yl]propanoic and 4-hydroxy-2-phenylpyrimidine-5-carboxylic acids. New 6-sulfanyl-substituted benzimidazo-[1,2-c]quinazolines were also prepared.     

One-pot synthesis of novel 1,2,3-triazole-pyrimido[4,5-c]isoquinoline hybrids and evaluation of their antioxidant activity

A series of novel pyrimido[4,5-c]isoquinolines (3a–3h) and 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinolines (4a–4h) were synthesized in good to excellent yields in the one-pot method. The reaction of 6-amino-1,3-dimethyluracil with different 2-iodo benzoyl chlorides using Pd catalyst in dimethylformamide afforded corresponding pyrimido[4,5-c]isoquinolines (3a–3h). One-pot reaction of pyrimido[4,5-c]isoquinolines with propargyl bromide and benzyl azide in THF at room temperature furnished 1,2,3-triazole-coupled pyrimido[4,5-c]isoquinoline (4a–4h). In vitro antioxidant activity examination revealed that compounds 4d and 4c found to exhibit potent antioxidant activity as compared to the standard drug Trolox with IC₅₀ values 6.02?±?0.6 and 12.18?±?0.9?µM, respectively.     

Synthesis of substituted dihydrobenzo[f]pyrimido[4,5-b]-quinolines as tetracyclic 5-deaza nonclassical folates

Cyclocondensation of 2,4,6-triaminopyrimidine ( 10 ) with chlorovinyl aldehyde 7 afforded the linear regioisomer 9,1 1-diamino-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 1 ) while the cyclocondensation of 2,6-diamino-4-hydroxypyrimidine ( 11 ) or 6-amino-2,4-dihydroxypyrimidine ( 12 ) with chlorovinyl aldehyde 7 was regiospecific affording the linear regioisomers 9-amino-11-oxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 2 ) and 9,11-dioxo-5,6-dihydrobenzo[f]pyrimido[4,5-c]quinoline ( 3 ) respectively. The linear structures of these compounds were established by ¹H nmr and ¹³C nmr spectral data.     

Synthesis of New Heterocyclic Systems on the Basis of 7-Benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthiridine-4-carbonitrile

Methods have been developed for the synthesis of new 8-amino-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine starting from 7-benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile. 8-Hydrazinyl-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine has been converted to isomeric pentacyclic structures with a triazole ring fused through the [c] side of the pyrimidine ring, and their Dimroth rearrangement has been accomplished in both acidic and basic media. New heterocyclic systems containing pyrrolo[1,2-a]pyrimidinone and pyrimido[1,2-a]azepinone fragments were obtained on the basis of the thieno-[2,3-c][2,7]naphthyridine derivative.     

Pyridazines. XXXV. Preparation of some novel pyrimido[4,5-c]pyridazine derivatives from 3-alkylamino- and 3-arylamino-4-pyridazinecarboxamides

Facile syntheses of pyrimido[4,5-c]pyridazine-5,7(6H,8H)diones 4 , pyrimido[4,5-c]pyridazin-5(8H)-ones 7–10 , and dihydropyrimido[4,5-c]pyridazin-5(6H)ones 5,6 starting from 3-chloro-4-pyridazinecarbonitrile 1 via aminocarbonitriles 2 and aminocarboxamides 3 are described. In addition, a convenient access to the new aminopyridazinecarbonitrile 11 from the chloronitrile 1, employing the tetrazolo[1,5-b]pyridazine 12 as the key intermediate, is reported.     

Cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines): synthesis, structure and mechanism of their formation

Reactions of 3-alkylamino-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with cyclohexyl- and cycloheptylamines in the presence of AgPy₂MnO₄ produce novel cycloalkano[1″,2″:4,5;4″,3″:4′,5′]bis(pyrrolo[2,3-c]pyrimido[5,4-e]pyridazines). Detailed information concerning the scope and mechanism of these transformations is discussed.     

Synthesis of pyrimido[6,1-a]isoquinolines via a one-pot, four-component reaction

An efficient one-pot synthesis of pyrimido[6,1-a]isoquinoline-1-carboxylate derivatives is described. This involves the four-component reaction between primary amines, alkyl acetoacetates, isoquinoline and trichloromethylchloroformate (diphosgene) under mild conditions at ambient temperature.     

Purines, pyrimidines, and related fused systems. 21. Oxidative amination of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione

Oxidative amination of 3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione with primary alkylamines and potassium amide in liquid ammonia gives rise to the corresponding 4-amino derivatives as the major products. The reactions with acyclic secondary amines are accompanied by annelation of the pyrrole moiety to the starting heterosystem to form 1-R-3-R"-6,8-dimethylpyrrolo[2",3";3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones. The reaction with piperidine as the aminating agent occurs exclusively as aminodehalogenation. The Sonogashira cross-coupling of 4-amino-3-chloro-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones with terminal alkynes affords 1-R-2-R"-6,8-dimethylpyrrolo[3",2";3,4]pyrimido[4,5-c]pyridazine-7,9(6H,8H)-diones.     

Studies on 6-[(dimethylamino)methylene]aminouracil: a facile one-pot synthesis of novel pyrimido[4,5-d]pyrimidine derivatives

The reactions of 6-[(dimethylamino)methylene]aminouracil 1, with various heterocumulenes such as aryl isocyanates and isothiocyanates give rise to novel pyrimido[4,5-d]pyrimidines in excellent yields, after elimination of dimethylamine from the (1:1) cycloadducts and tautomerisation. This procedure provides a convenient method for direct synthesis of pyrimido[4,5-d]pyrimidine derivatives under thermal conditions.     

N-bromosuccinimide in heterocyclic synthesis. Synthesis of pyrazolo[3,4-d]pyrimidines,Pyrimido[5,4-e]-as-triazines,and pyrimido[4,5-c]pyridazines from 6-arylidenehydrazino-1,3-dimethyluracil derivatives

Reactions of 6-arylidenehydrazino-1,3-dimethyluracil derivatives with N-bromosuccinimide leading to pyrazolo[3,4-d]pyrimidines, pyrimido[5,4-e]-as-triazines, and pyrimido[4,5-c]pyridazines are described.     

Synthesis and reactions of some new selenolo[2,3-<Emphasis Type="Italic">c</Emphasis>]pyridazines

New series of selenolo[2,3-c]pyridazine and pyrimido[4',5':4,5]selenolo[2,3-c]pyridazine derivatives were prepared from 4-cyano-5,6-diphenylpyridazine-3(2H)-selenone. Elemental analysis, IR, ¹H NMR, and mass spectra confirmed the structures of the newly synthesized compounds.     

Synthesis of new polycyclic systems containing the pyrimido[2,1-a]phthalazine skeleton

The synthesis of new polyheterocycles containing the pyrimido[2,1-a]phthalazine system 5, 6 and 7 , obtained by condensation of phthalic anhydride with the appropriate hydrazides 2, 3 and 4 , respectively, are reported. It was also synthesized the 14H-[1]Benzothieno[3′,2′:4,5]pyrimido[2,1-a][1,2,4]triazolo[4,3-c]phthalazin-14-one (16).     

Cyclic guanidines: Synthesis of 4,6,7,8-tetrahydro-1H-imidazo[1,2-a]pyrazolo[3,4-d]pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo[3′,4′:4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones

The synthesis of potential platelet aggregation inhibitors 4,6,7,8-tetrahydroimidazo[1,2-a]pyrazolo[3,4-d]-pyrimidin-7-ones and 1,4,6,7,8,9-hexahydropyrazolo[3′,4′:4,5]pyrimido[2,1-c] [1,2,4]triazin-7-ones derivatives is described starting from 4,6-dichloropyrazolo[3,4-d]pyrimidines.     

Synthesis of 5,8-Diamino-Substituted Pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidines and Pyrimido[4′,5′:4,5]thieno[2,3-<Emphasis Type="Italic">c</Emphasis>]isoquinolines

Ethyl 1-amino-8,8-dimethyl-5-(piperidin-1-yl)-8,9-dihydro-6H-pyrano[4,3-d]thieno[2,3-b]pyridine-2-carboxylate and ethyl 1-amino-5-(piperidin-1-yl)-6,7,8,9-tetrahydrothieno[2,3-c]isoquinoline-2-carboxylate reacted with benzoyl isothiocyanate to give the corresponding 1-thioureido derivatives which underwent cyclization to 2,2-dimethyl-5-(piperidin-1-yl)-10-thioxo-1,4,10,11-tetrahydro-2H-pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidin-8(9H)-one and 5-(piperidin-1-yl)-10-thioxo-1,2,3,4,10,11-hexahydropyrimido-[4′,5′:4,5]thieno[2,3-c]isoquinolin-8(9H)-one. The cyclization products were converted into 8-chloro derivatives, and the chlorine atom therein was replaced by various amines.