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.     

Diastereoselective one-pot synthesis of novel ABCD-fused chromeno[2,3-d]pyrazolo[3,4-b]pyridines

A new aspect concerning chromone chemistry leading to the one-pot synthesis of functionalized novel ABCD-fused chromenopyrazolopyridines has been described. The synthesis involves a multicomponent reaction of chromone-3-benzoylhydrazones with isocyanides and acetylenedicarboxylates, whereupon novel complex tetracyclic benzopyrone derivatives containing three stereogenic centres were formed. The structure elucidation of the products was accomplished by 1D and 2D NMR experiments and confirmed by X-ray crystallographic analysis. Full assignment of all ¹H and ¹³C NMR chemical shifts has been unambiguously achieved. The reaction mechanism is also discussed. In addition, eight chromenopyrazolopyridine derivatives were tested for possible biological activity (antioxidant and lipid peroxidation inhibition).     

Synthesis of azepino[3,4b]indoles via the Plancher rearrangement

The reaction of benzyl 3-formylpiperidine-1-carboxylate and aryl hydrazines under standard Fisher Indole conditions followed by reductive work-up affords azepino[3,4b]indoles in moderate to good yields. The products are proposed to be derived via a Plancher rearrangement [(a) Plancher, G. Gazz. Chim. Ital. 1898, 28, II, 374; (b) Plancher, G. Atti. Accad.Lincei1900, 9, 5, 115; (c) Boyd-Barrett, H. S. J. Chem. Soc.1932, 321].     

Synthesis of benz[5,6]azepino[4,3-b]indoles by 1,7-electrocyclisation of azomethine ylides

A new, general route to the benz[5,6]azepino[4,3-b]indole ring system has been developed via the 1,7-dipolar electrocyclisation reactions of azomethine ylides derived from easily available 3-formyl indole derivatives. The intermediacy of azomethine ylides was shown by the trapping of the proposed α,β:γ,δ-conjugated dipole with N-phenylmaleimide.     

Regioselective formylation of pyrazolo[3,4-b]pyridine and pyrazolo[1,5-a]pyrimidine systems using Vilsmeier-Haack conditions

Regioselective formylation behavior has been found in the reaction of pyrazolo[3,4-b]pyridines and pyrazolo[1,5-a]pyrimidines via Vilsmeier-Haack conditions. While the 4,5- and 6,7-dihydro derivatives afforded pyrazolo[3,4-b]pyridine-5-carbaldehydes and 4,7-dihydropyrazolo[1,5-a]pyrimidine-3,6-dicarbaldehydes, respectively, the aromatic analogs rendered the pyrazolo[1,5-a]pyrimidine-3-carbaldehyde only, and no reaction took place at the pyrazolopyridine derivatives.     

Diels-Alder reactions of pyrrolo[3,4-b]porphyrins

In the presence of excess dimethylacetylene dicarboxylate (DMAD), nickel(II) pyrrolo[3,4-b]porphyrins undergo both Diels-Alder cycloaddition and Michael addition in toluene to give two bis-adducts, identified as compounds 4 and 5; the reaction can be accelerated by the addition of Lewis or Brønsted-Lowry acids. Refluxing the reaction mixture in 1,2,4-trichlorobenzene (220 °C) leads to a nickel(II) monobenzoporphyrin 2 as the main product. The structure of compound 4 was confirmed by X-ray crystallography.     

Efficient synthesis of trisubstituted [1]benzopyrano[4,3-b]pyrrol-4(1H)-one derivatives from 4-hydroxycoumarin

Various trisubstituted [1]benzopyrano[4,3-b]pyrrol-4(1H)-one derivatives have been synthesized from 4-hydroxycoumarin with a 30-40% yield over six steps. The key step of the synthesis is a base-promoted intramolecular cyclization of enamines 5, followed by dehydration to generate the fused pyrrole ring.     

Pd-Mediated synthesis of 7H-benzo[3,4]azepino[1,2-a]indole-6-carboxylic acid derivatives from indole-containing Baylis-Hillman adducts

We synthesized novel tetracyclic fused indole derivatives via the intramolecular Heck reaction of indole-containing Baylis-Hillman adducts in good to moderate yields.     

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.     

Convenient synthesis of pyrazolo[3,4-b]pyridin-3-ones and pyrazolo[3,4-b]pyridine-5-carbaldehyde using vinamidinium salts

An expedient method for the synthesis of 2-phenyl-5-aryl-2,3-dihydropyrazolo[3,4-b]pyridin-3-ones and 2-phenyl-3-oxo-2,3-dihydropyrazolo[3,4-b]pyridine-5-carbaldehyde in a single-step via condensation of vinamidinium salts with 3-amino-1-phenyl-2-pyrazolin-5-one is described.     

Chemical reactivity of [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts

The chemical reactivity of the [1,2,3]triazolo[1,5-a]- and [1,5-c]-pyrimidinium salts towards morpholine, water and sodium methoxide have been studied. Among others, new 1-aza and 2-azabutadienes substituted by a [1,2,3]-triazole ring were obtained in the course of the opening of the positively charged pyrimidine ring.     

Regiocontrolled synthesis of 3- and 5-aminopyrazoles,pyrazolo[3,4-d]pyrimidines,pyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]quinolinones as MAPK inhibitors

Microwave irradiation of a hydrazine and 3-methoxyacrylonitrile, ethoxymethylenemalononitrile or ethyl acetoacetate provides rapid access to 3- or 5-substituted pyrazoles in excellent yield and with total regiocontrol in a process that can be switched from one regioisomer to the other by choice of conditions. Subsequent reaction, either by microwave-assisted hydrolysis and cyclocondensation with formamide, Hantzsch-type three-component reaction with an aldehyde and ketone, or by cyclocondensation with 2-nitrobenzaldehyde, provides the pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-b]pyridine or pyrazolo[3,4-b]quinolin-4-one framework, respectively, of inhibitors of mitogen-activated protein kinases.     

Microwave-assisted and iodine mediated synthesis of 5-n-alkyl-cycloalkane[d]-pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and cyclic ketones

5-n-Alkylcycloalkane[d]pyrazolo[3,4-b]pyridines were prepared by a microwave-assisted cyclocondensation reaction between 5-aminopyrazoles and cyclic ketones under solvent-free conditions and catalyzed by iodine. This procedure provides a simple one-step and environmentally friendly methodology with good yields for the synthesis of these compounds.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Synthesis of novel dipyrazolo[3,4-b:3,4-d]pyridines and study of their fluorescence behavior

A convenient route was successfully developed for the synthesis of novel heterocycles such as pyrazolo[3,4-h][1,6]naphthyridine and dipyrazolo[3,4-b:3,4-d]pyridine (DPP) from pyrazolo[3,4-b]pyridine in good yield. The DPP derivatives synthesized were further studied for their fluorescence properties.     

Synthesis of 4-amino-3-oxo-tetrahydroazepino[3,4-b]indoles: new conformationally constrained Trp analogs

The synthesis of tryptophan analogs is reported in which the conformation has been constrained by formation of a seven-membered lactam. Boc-protected 2′-formyl tryptophan was obtained by SeO₂ oxidation of Boc-tetrahydro-β-carboline-3-carboxylic acid. Reductive amination was performed with a variety of amines and amino acid esters using sodium cyanoborohydride, followed by ring closure to the target compounds. The constrained Trp derivative has been incorporated into the endomorphin-1 opioid peptide sequence to probe the bioactive conformation.     

Acylation d'aminopyrazoles: formation de pyrazolo[3,4-b]pyridines,pyrazolo[3,4-d]pyrimidines et dipyrazolo[3,4-b:4',3'-e]pyridines

A new method to obtain pyrazoloazines has been developped from the reaction between acetic anhydride or benzoyl chloride and 1,3-dimethyl-5-aminopyrazole. The structure of the new products has been established and an explanation for their origine has been proposed.     

Zinc triflate-catalyzed synthesis of pyrazino[2,1-b]quinazoline-3,6-diones

Using zinc triflate, the direct one-pot double cyclodehydration of linear tripeptides to the total synthesis of pyrazino[2,1-b]quinazoline-3,6-diones (1a-l) on solid support was achieved with good overall yields in short reaction time. These syntheses of the pyrazino[2,1-b]quinazoline-3,6-diones were conveniently achieved in only three steps, starting from the amino acid-bound Wang resin.     

2,3-Disubstituted pyrrolo[2,3-b]quinoxalines via aminopalladation-reductive elimination

2,3-Disubstituted pyrrolo[2,3-b]quinoxalines have been prepared in good to high yield through the reaction of 2-alkynyl-3-trifluoroacetamidoquinoxalines with aryl and vinyl halides or triflates in the presence of Pd(PPh₃)₄ and K₂CO₃ in MeCN at 100 °C.     

New four-component reactions in water: a convergent approach to the metal-free synthesis of spiro[indoline/acenaphthylene-3,4′-pyrazolo[3,4-b]pyridine derivatives

New four-component domino reactions are described that allow the one-pot synthesis of spiro[indoline/acenaphthylene-3,4′-pyrazolo[3,4-b]pyridine derivatives from the reaction of phenylhydrazine, 3-aminocrotononitrile, isatin/acenaphthylene-1,2-dione, and cyclic 1,3-dicarbonyl compounds, including cyclohexane-1,3-diones, barbituric acid, and 2-thioxodihydropyrimidine-4,6(1H,5H)-dione, in the presence of (±)-camphor-10-sulfonic acid (CSA). These processes take place in water and involve the generation of two rings and five new bonds (two C-C, two C-N and one CN) in a single synthetic operation, with expedient work-up and diminished waste generation due to the absence of extraction and purification steps.