Preparation of novel pyridine-fused tris-heterocycles; pyrido[4,3-e]pyrrolo-/pyrido[4,3-e]furano[2,3-c]pyridazines and pyrido[3,4-b]pyrrolo[3,2-d]pyrrole

Three novel pyrido-fused tris-heterocycles have been prepared based on a Suzuki coupling and subsequent cyclisation approach. Pyrido[4,3-e]pyrrolo[2,3-c]pyridazine (3b, 77%) and pyrido[4,3-e]furano[2,3-c]pyridazine (5b, 76%) were obtained by intramolecular diazocoupling. Successful diazocoupling of furan (5b) is thus reported for the first time by NOBF₄ generation of the diazonium intermediate. N-TIPS-pyrido[3,4-b]pyrrolo[3,2-d]pyrrole (TIPS-4b) was synthesised by thermal cyclisation of pyridyl nitrene in considerably higher yield (71%) than previously experienced from similar cyclisations, due to TIPS-activation.     

Synthesis of 1- and 2-Carbamoylalkyl-2,3-dihydro-1H-indole and 9-Carbamoylalkyl-2,3,4,4a,9,9a-hexahydro-1H-carbazole Derivatives

Treatment of 1,2,3,9a-tetrahydro-9H-imidazo- and 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one derivatives with formic acid gave 1-carbamoylalkyl-2,3,3-trimethyl-2,3-dihydro-1H-indoles. 9-Carbamoylmethyl- and 9-(2-carbamoylethyl)-4a-methyl-2,3,4,4a,9,9a-hexahydro-1H-carbazoles were prepared from 5,6,7,7a-tetrahydro-1H,4H-imidazo- and 1,2,6,7,8,8a-hexahydro-5H-pyrimido[2,1-k]carbazolones in a similar manner. Synthesis of 2-(2-carbamoylpropyl)-2,3,3-trimethyl-2,3-dihydro-1H-indole was carried out by reduction of 1,3-dihydrospiro[2H-indolo-2,2'-piperidine] derivative with Zn in acetic acid solution.     

Synthesis of 2,3-diaryl-5H-imidazo[2,1-a]isoindol-5-ones via the one-pot reaction of 1,2-diketones, 2-formylbenzoic acids, and ammonium acetate

We describe a new one-pot synthesis of 2,3-diaryl-5H-imidazo[2,1-a]isoindol-5-ones via the reaction of 1,2-diketones, 2-formylbenzoic acids, and ammonium acetate in acetic acid under reflux conditions and in the absence of a catalyst.     

New convenient synthesis of 2,3-diaminothieno[2,3-d]pyrimidin-4(3H)-one derivates from substituted alkyl 2-(1H-tetrazol-1-yl)thiophene-3-carboxylates

4,5-Disubstituted and 4-substituted alkyl 2-amino-thiophene-3-carboxylates react with triethyl orthoformate and sodium azide in acetic acid to yield new 2-(1H-tetrazol-1-yl)-4-R¹-5-R²-thiophene derivates. It was established that the reaction of these tetrazoles with hydrazine generates the insufficiently studied 2,3-diaminothieno[2,3-d]pyrimidin-4(3H)-one system. It is significant that the reaction mentioned above is the unique tetrazole ring cleavage under the action of hydrazine.     

Synthesis and structure of some thienopyrimidine derivatives

A series of substituted thieno[2,3-d]pyrimidines was synthesized starting from ethyl-2-amino-4-isopropylthiophene-3-carboxlate. Reaction of 2-hydrazino-5-isopropyl-thieno[2,3-d]pyrimidin-4(3H)-one and its 3-methyl analogue with different reagents afforded thieno[2,3-d]triazolo[4,3-a]pyrimidines and thieno[3,2-e]triazolo[4,3-a]pyrimidines, beside open chain derivatives. Correspondence: Atef A. Hamed, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El Koam, Egypt.     

Synthesis of 2-aryl-1,2,3,4-tetrahydroquinazolin-1-ols and their conversion to 7-aryl-9H-6-oxa-5,8-diaza-benzocycloheptenes

2-Aminobenzylamine was reacted with corresponding aromatic or heteroaromatic aldehydes to give 1,2,3,4-tetrahydroquinazolines 1 the oxidation of which with H₂O₂-tungstate in methanol led to the formation of the corresponding 1,2,3,4-tetrahydroquinazolin-1-ols 2. A one-pot procedure involving the treatment of the in situ formed quinazoline 1 with H₂O₂-tungstate again led to the formation of 2. Compounds 2 react with 2 equiv of aryl isocyanate in toluene at room temperature to produce compounds 3. The probable mechanism of the ring-expanding carbamoylation of quinazolin-1-ols 2 to 6-oxa-5,8-diaza-benzocycloheptenes 3 is discussed.     

Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: routes towards condensed thieno[2,3-b]pyridines

Synthetic approaches towards new condensed thienopyridine ring systems including furo[2,3-b]thieno[3,2-e]pyridines, bisthieno[2,3-b:3′,2′-e]pyridines, 5H-chromeno[2,3-b]thieno[3,2-e]pyridines, 5H-benzo(f)chromeno[2,3-b]thieno[3,2-e]pyridines have been achieved by application of intramolecular 4+2 cycloaddition reactions of suitably designed thieno[2,3-e][1,2,4]triazines tethered with alkene or alkyne terminals.     

Synthesis of a 5-alkoxypyrido[4,3-d]pyrimidin-4(3H)-one derivative via a regioselective Meisenheimer N-oxide rearrangement

The synthetic strategy towards a 5-alkoxypyrido[4,3-d]pyrimidin-4(3H)-one is described utilizing a selective N-oxidation and subsequent regioselective Meisenheimer N-oxide rearrangement as key steps.     

The reaction of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones with dinucleophilic reagents: a convenient route to fluoroalkylated nitrogen-containing tricyclic compounds

The reactions of 2-(1-hydropolyfluoro-1-alkenyl)-4H-3,1-benzoxin-4-ones (2) with hydrazine hydrate and phenyl hydrazine were investigated. The reaction of 2 with hydrazine hydrate in ethanol under reflux condition readily gave 2-fluoroalkyl-4H-pyrazolo[5,1-b]quinazolin-9-ones (3) in high yields. The reaction of 2 with phenyl hydrazine, however, resulted in the formation of 2-(2-phenyl-5-fluoroalkyl-2H-pyrazol-3-yl) benzoic acids (7). Further treatment of 7 with PPA gave 1-phenyl-4,9-dihydro-3-fluoroalkyl-1H-pyrozolo[3,4-b]quinolin-4-ones (4) in 65-80% overall yields.     

Synthesis of novel 2,3-substituted-2,4-dihydro-pyrazolo[4,3-d]pyrimidine-5,7-diones

Novel 2,3-substituted-2,4-dihydro-pyrazolo[4,3-d]pyrimidine-5,7-diones were successfully synthesized with moderate to good yields using a new synthetic approach. The structures of the regio-isomers in this series were determined by single crystal X-ray analysis and NMR spectra.     

Synthesis of new fluorescent building blocks via the microwave-assisted annulation reaction of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid and its derivatives

The reaction of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid and its derivatives was employed for the preparation of novel fluorescent building blocks. Treatment of 1,1,2-trimethyl-1H-benzo[e]indole with acrylic acid, acrylamide or tert-butyl acrylate in an autoclave or a microwave reactor at 180–200 °C afforded benzo[e]pyrido[1,2-a]indole derivatives. Various chemical transformations of the latter compounds have been performed to yield functionalized benzo[e]indole scaffolds. The structure assignments were based on data from ¹H and ¹³C NMR spectroscopy and single crystal X-ray analyses. The optical properties of the obtained benzo[e]indoline derivatives were studied by UV–vis and fluorescence spectroscopy.     

Synthesis of 5,8-dimethoxynaphtho[2,3-c]furan-4(9H)-one

The synthesis of the title compound, which shares its skeleton with a number of biologically active natural products, is described. The key steps are construction of a 3,4-disubstituted furan by a tandem Diels-Alder-retro-Diels-Alder reaction of an alkyne with 4-phenyloxazole, and an intramolecular Friedel-Crafts acylation.     

A rapid and convenient synthesis of novel 1-imino-2,3-dihydro-1H-pyrazino[2,1,-b]quinazolin-5-ones

Exploring original approaches for the synthesis of therapeutic agents having a quinazoline part, we discovered that novel 3,4-dihydro-2H-pyrazino[2,1,-b]quinazolines (3) may be rapidly and easily obtained via the chemistry of 4,5-dichloro-1,2,3-dithiazolium chloride (1). Our synthetic approach of this reaction is described with the aim of obtaining a well-controlled access to this very rarely described pyrazino[2,1,-b]quinazoline skeleton.     

Reactivity of the Mitsunobu reagent toward 3-formylchromones: a strategy for the one-pot synthesis of chromeno[2,3-c]pyrazolines and chromeno[2,3-e]tetrazepines

The zwitterionic intermediates generated from dialkyl azodicarboxylates and triphenylphosphine displayed excellent reactivity toward 3-formylchromones to afford chromeno[2,3-c]pyrazolines and chromeno[2,3-e]tetrazepines.     

A facile synthesis and fungicidal activities of novel fluorine-containing pyrido[4,3-d]pyrimidin-4(3H)-ones

Sixteen novel 2-substituted-5,8,9-trimethyl-3-(4-fluoro-substituted)phenyl-thieno[3′,2′-5,6] pyrido[4,3-d]pyrimidin-4(3H)-ones 5a-5p were designed and have been successfully synthesized via tandem aza-Wittig and annulation reactions of the corresponding iminophosphorances 1, para-fluoro phenyl isocyanate, and substituted phenols or amines in 73-90% isolated yields. Their structures were clearly verified by IR, ¹H NMR, EI-MS spectroscopy and elemental analysis, and in the case of compound 5a, analyzed by single-crystal X-ray diffraction further. The results of preliminary bioassay indicated that some compounds possess inhibition activities against Rhizoctonia solani and Botrytis cinereapers at a dosage of 50 mg/L.     

Synthesis of 9-arylamino- and (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles by reactions of 2-(pyrrol-1-yl)benzaldehydes with aryl amines

Heating mixtures of 2-(pyrrol-1-yl)benzaldehydes and aryl amines under argon afforded 9-arylamino-9H-pyrrolo[1,2-a]indoles, via cyclization of the resulting 2-(pyrrol-1-yl)benzaldimine intermediates. Heating in the presence of oxygen afforded (Z)-9-arylimino-9H-pyrrolo[1,2-a]indoles, which were successfully hydrolyzed with hydrochloric acid to give pyrrolo[1,2-a]indol-9-ones.     

1-Ethyl-1H-3-nitrobenzopyrano[4,3,2-cd]isoindole: a novel heterocyclic ring system bearing an unusually labile deuterium-exchangeable aromatic proton

The ease of deuterium exchange of the aromatic H2 of the novel heterocycle 1-ethyl-1H-3-nitrobenzopyrano[4,3,2-cd]isoindole was studied by NMR and theoretical calculations.     

Probes for narcotic receptor mediated phenomena. Part 31: Synthesis of rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-10-ol, and azocine-8-ol, the ortho-c and the para-c oxide-bridged phenylmorphan isomers

Two of the 12 possible oxide-bridged phenylmorphans, were synthesized, rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-10-ol (7) (the ortho-c compound), and rac-(3R,6aS,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzofuro[2,3-c]azocine-8-ol (8) (the para-c compound). Single-crystal X-ray diffraction studies indicated that the dihedral angle between the least squares planes through the phenyl ring and the atoms C₁, C_11a, C₁₂, and C₃ in the piperidine ring in both 7·CHCl₃ and 8·HBr was 6.9°. The C₁₂-C_6a-C_6b-C_10a torsion angle was found to be 139.3° for both compounds. The angular relationship between the phenolic ring and the piperidine ring in phenylmorphans that interact with specific opioid receptors as agonists or antagonists is of considerable theoretical interest.     

New and efficient RCM in pyridinic series: synthesis of 2H-dihydropyrano- or 2,3H-dihydrooxepino[3,2-b]pyridines

A new and very efficient route to polycyclic heterocycles with isosteric replacement of benzene by pyridine is reported. This strategy involving the RCM reaction in pyridinic series as a keystep allows us to prepare 2H-dihydropyrano- or 2,3H-dihydrooxepino[3,2-b]pyridines 1 and 2 in very good overall yields (47% and 44%, respectively).