Synthetic approaches to 5,7-disubstituted imidazo[5,1-f][1,2,4]triazin-4-amines

The preparation of 5,7-disubstituted imidazo[5,1-f][1,2,4]triazin-4-amines, exemplified by 5-[3-(benzyloxy)phenyl]-7-cyclobutylimidazo[5,1-f][1,2,4]triazin-4-amine, was developed through a linear and three convergent synthetic strategies, with the latter providing the greatest flexibility for diversification at the 5-position at the last step of the synthesis.     

Synthesis of novel 1-methyl-1H-pyridazino[3,4-b]indoles

New synthetic pathways have been elaborated to 1-methyl-1H-pyridazino[3,4-b]indoles starting from halopyridazin-3(2H)-ones. Suzuki cross-coupling reaction of chloro, iodo, dichloro, and dibromo substituted pyridazin-3(2H)-ones with 2-pivaloylaminophenylboronic acid followed by hydrolysis of the amide and subsequent ring closure via condensation gave fused indoles. Some of these compounds showed biological activity as antitrypanosomal agents.     

Synthesis of a new compound family, 1-aryl-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-ones

Representatives of a new family, 1-aryl-3H-pyrrolo[2,1-d][1,2,5]triazepin-4(5H)-ones have been synthesized at our laboratory as bioisosters of biologically active 1-aryl-2,3-benzodiazepine-4-ones. The efficient synthetic route described applies the synthesis of 2-(2-aroylpyrrol-1-yl)acyl hydrazides followed by ring closure under acidic conditions. The N(3)-unsubstituted title compounds thus obtained can optionally be N-alkylated rendering the preparation of variously substituted derivatives possible. Scope and limitations of the new protocol and some interesting side reactions are also discussed in detail.     

Synthesis of 2,6-disubstituted pyrido[2,3-b][1,4]oxazines

A new preparative method for pyrido[2,3-b][1,4]oxazines from 6-substituted 3-nitro-2-pyridones is demonstrated. This method consists of two steps: O-alkylation and reductive cyclization. In the former step, the bulkiness of both starting nitropyridones and C2 reagents is found to be essential for avoiding N-alkylation, which undergoes O-alkylation efficiently. The subsequent reductive cyclization affords pyridoxazines with carbon substituents at both the 2- and the 6-positions that have not been available.     

Niementowski-type synthesis of pyrido[3,2-e][1,2,4]triazines: potent aza-analogs of pyrido[2,3-b]pyrazine fungicides

Novel trisubstituted pyrido[3,2-e][1,2,4]triazines have been found to possess similar biological activity to the corresponding pyridopyrazine fungicides against important phytopathogens such as Mycosphaerella graminicola (wheat leaf blotch), Magnaporthe grisea (rice blast), and Rhizoctonia solani (rice sheath blight). They have been prepared for the first time from a monocyclic triazine by Niementowski-type ring condensation.     

新型2-氧代-1,2,4-三唑并[3,2-d][1,5]苯并氧氮杂类稠杂环的合成

将取代色满酮(1)与芳肼反应生成的腙与HNCO发生[3+2]环加成反应,加成产物(2)经氧化得到偕偶氮异氰酸酯(3).化合物3在HBF4的催化下发生环化-重排反应,得到新颖的三环系2-氧代-1,2,4-三唑并[3,2-d][1,5]苯并氧氮杂化合物5a～5g.     

A convenient synthesis of new pyrido[3,2-e][1,4]diazepine-2,5-diones and pyrido[2,3-e][1,4]diazepine-2,5-diones

A convenient synthesis of a series of pyrido[3,2-e][1,4]-diazepine-2,5-diones 8 and pyrido[2,3-e][1,4]diazepine-2,5-diones 9, is reported using the condensation of α-amino acid methyl ester derivatives with 1H-pyrido[3,2-d][1,3]oxazine-2,4-dione and 1H-pyrido[2,3-d][1,3]oxazine-2,4-dione. Compounds 8 and 9 were also synthesized by peptide coupling of α-amino acid methyl ester derivatives with β-amino acids (2 or 3) followed by the cyclisation in tetrahydrofuran with sodium hydride (NaH).     

Novel regio- and stereo-selectivity: synthesis of dihydropyrrolo[1,2-f]phenanthridines via isocyanide-based multicomponent reaction

The novel one-pot three-component reactions of the zwitterions generated in situ from three isocyanides and 2-arylidenemalononitriles with phenanthridine via 1,3-dipolar cycloaddition are described. The reactions afforded the corresponding dihydropyrrolo[1,2-f]phenanthridine derivatives in good yields without using any catalyst and activation. The stereochemistry of the final products was confirmed by single-crystal X-ray diffraction analysis.     

Intramolecular amidation: synthesis of novel imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of 2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde and 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.     

Synthesis of novel pyrido[2,3-e][1,3]oxazines

The preparation of novel pyrido[2,3-e][1,3]oxazines starting from 3-hydroxy-pyridine-2-carbonitrile, N-aralkoxy-3-hydroxy-pyridine-2-carboxamides and 3-hydroxy-pyridine-2-carboxylic acid hydrazides is described.     

First total syntheses of the 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines annoretine and litebamine

We describe here the first total synthesis of the two natural 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines, annoretine and litebamine, from [2-(2-styrylphenyl)ethyl]methylcarbamic acid ethyl esters. The key steps were the Bischler-Napieralski cyclization to form the isoquinoline unit and photocyclization of the resulting 2-methyl-5-styryl-3,4-dihydro-2H-isoquinolin-1-ones to 2-methyl-3,4-dihydro-2H-naphtho[2,1-f]isoquinolin-1-ones.     

A new strategy for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines

A series of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of aldehyde N-(1,3-diphenylpyrazolo[3,4-d]pyrimidin-4-yl)hydrazones. Dimroth rearrangement of such a series yielded pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.     

Access to ring-fused azepino[3,4-b]indole-1,5-dione derivatives by ring-closing olefin metathesis

The new ring-fused azepino[5,6-b]indole derivatives 3, 4 and 5 were prepared from diene precursors 8, 9, 13 and 15 in fair yields via a final ring-closing olefin metathesis.     

新型2-氧代-1,2,4-三唑并[3,2-d][1,5]苯并氧氮杂类稠杂环的合成

将取代色满酮 ( 1 )与芳肼反应生成的腙与 HNCO发生 [3 +2 ]环加成反应 ,加成产物 ( 2 )经氧化得到偕偶氮异氰酸酯 ( 3 ) .化合物 3在 HBF4 的催化下发生环化 -重排反应 ,得到新颖的三环系 2 -氧代 -1 ,2 ,4-三唑并[3 ,2 -d][1 ,5 ]苯并氧氮杂化合物 5 a～ 5 g     

Synthetic studies on KF-alumina-catalysed reaction of substituted and unsubstituted aryl-oxoketene dithioacetals and 1H-pyrazone-5(4H)-one: a convenient synthesis of pyrazolo[3,4-b]pyridine and pyrazolo[1,5-a]pyrimidine

The procedures described herein provide a facile method for the synthesis of pyrazolo[3,4-b]pyridine and pyrazolo[1,5-a]pyrimidine by reacting N-substituted or unsubstituted-pyrazol-5(4H)-one, aryl-oxoketene dithioacetals and alkyl amide. The products were obtained in moderate to good yield. The effects of the solvents and substitution have also been described.     

DNMR, DFT and preparative study on the conformation of (Z)-4,5,6,7-tetrahydropyrazolo[1,5-e]benzo[g][1,5]diazonin-8-ones and (Z)-4,5-dihydropyrazolo[1,5-d]benzo[f][1,4]diazocin-7(6H)-ones

By means of base-catalyzed ring enlargement of triazaindenoindenes and pentalenoindenes obtained from anhydride-induced ring transformation of 3,4-dihydro-2H-pyrimido- and 2,3-dihydroimidazo[2,1-a]phthalazinium-olates, respectively, a series of pyrazolo[1,5-e]benzo[g][1,5]diazonin-8-ones and pyrazolo[1,5-d]benzo[f][1,4]diazocin-7(6H)-ones were obtained. Alternative pathways and energetics for the ring inversion of symmetrically substituted medium-size ring systems were determined by combined use of DNMR measurements and B3LYP/6-31G(d,p) calculations using the IEFPCM solvent model. One pyrazolobenzodiazonine carrying hydrogen at the C1 position was found to undergo facile ring inversion by a two-step mechanism, while 1-Me and 1-Ph substituents rendered complete rigidity to this ring system. A three-step mechanism was revealed for the ring inversion of the two studied pyrazolobenzodiazocines with energetics practically invariant to the investigated C1-substituents (H and Me). The attempted RCM of the N,O-diallyl derivative of a selected rigid model effected by Grubbs II catalyst led to deallylation and olefin isomerization avoiding the formation of bridged products with enhanced skeletal strain. A tolerable degree of ring strain associated with negligible skeletal distortion could be introduced into the same benzodiazonine by N,O-dialkylation with 1,3-bis(bromomethyl)benzene.     

An efficient diastereoselective synthesis of spiro pyrido[2,1-b][1,3]oxazines via a novel pyridine-based three-component reaction

The zwitterions generated from pyridine and dialkyl acetylenedicarboxylate (DAAD) reacted with benzofuran-2,3-diones to form highly substituted spiro pyrido[2,1-b][1,3]oxazines in good to high yields without using a catalyst.     

A facile synthesis and highly atom economic 1,3-dipolar cycloaddition of hexahydropyrido[3,4-c][1,5]benzothiazepines with nitrile oxide: stereoselective formation of hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines

A series of new 2-methyl-11-aryl-4-[(E)-arylmethylidene]-1,2,3,4,11,11a-hexahydropyrido[3,4-c][1,5]benzothiazepines were obtained by the reaction of o-aminothiophenol and (E)-1-methyl-3,5-bis(arylidene)-4-piperidones in the presence of a catalytic amount of acetic acid under solvent-free microwave irradiation. These dipolarophiles undergo a highly atom economic 1,3-dipolar cycloaddition with nitrile oxide to afford a series of novel 6-methyl-1-phenyl-8-aryl-4-[(E)-arylmethylidene]-4,5,6,7,7a,8-hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines stereoselectively.     

Synthesis of 2-benzylimidazo[2,1-b][1,3]benzothiazoles through palladium-catalyzed heteroannulation of acetylenic compounds

The reaction of 2-imino-3-(2-propynyl)-1,3-benzothiazole with various iodobenzenes in the presence of a palladium catalyst leads to the production of 2-benzylimidazo[2,1-b][1,3]benzothiazoles.     

Enantiospecific synthesis of 5-phenylpyrrolo[2,1-c][1,4]benzodiazepines

Enantiomerically pure 5-phenylpyrrolo[2,1-c][1,4]benzodiazepines were synthesized starting from 2-aminobenzophenones and 2-amino-4-methoxyxanthone, using l-proline as a chiral building block.