Synthesis Of Indazoles Research Articles

Diazo Activation with Diazonium Salts: Synthesis of Indazole and 1,2,4-Triazole.

A donor/acceptor diazo activation strategy, processing via condensation using diazonium salts without the addition of any other catalysts or reagents, is reported. The diazenium intermediate was found to undergo cyclization to give indazoles in excellent yields. Alternatively, in the presence of nitriles, substituted 1,2,4-triazoles were obtained in good to excellent yields. This interesting diazenium route provides a new approach to achieve complex heterocycle synthesis under mild conditions.

Rhodium(III)-Catalyzed Oxidative Annulation of Ketoximes with Sulfonamide: A Direct Approach to Indazoles.

A rhodium(III)-catalyzed intermolecular C-H amination of ketoxime and iodobenzene diacetate-enabled N-N bond formation in the synthesis of indazoles has been developed. A variety of functional groups were well tolerated, providing the corresponding products in moderate to good yields. Moreover, the nitro-substituted ketoximes are well compatible in this reaction, leading to the corresponding products in moderate to good yields.

Synthesis of Fluorescent Indazoles by Palladium-Catalyzed Benzannulation of Pyrazoles with Alkynes

The synthesis of indazoles from pyrazoles and internal alkynes is described. Instead of complex benzenoid compounds, readily available pyrazoles were used for the preparation of indazoles by reaction of the C-H bonds of the heterocyclic ring. Oxidative benzannulation was also applied to imidazoles, providing benzimidazoles. This convergent strategy enabled alteration of the photochemical properties of benzo-fused diazoles by varying the substituents at the benzene ring, thus leading to the development of tetraarylindazoles as new fluorophores.

Synthesis of Indazoles and Indoles from Azobenzenes through C–H Activation

Synthesis of Indazoles and Indoles from Azobenzenes through C–H Activation

ChemInform Abstract: Copper(I) Oxide‐Mediated Cyclization of o‐Haloaryl N‐Tosylhydrazones: Efficient Synthesis of Indazoles.

AbstractThe synthesis of indazoles from E/Z‐mixtures of o‐haloraryl‐N‐sulfonylhydrazones is reported.

Synthesis of Indazoles by Oxidative N–N Bond Formation

Synthesis of Indazoles by Oxidative N–N Bond Formation

ChemInform Abstract: Rhodium(III)‐Catalyzed N‐Nitroso‐Directed C—H Addition to Ethyl 2‐Oxoacetate for Cycloaddition/Fragmentation Synthesis of Indazoles.

AbstractA Rh‐catalyzed N‐nitroso directed C‐H functionalization of N‐substituted N‐nitrosoanilines (I) and (V) with ethyl glyoxylate to yield ortho‐disubstituted products (III) and (VI) is developed.

ChemInform Abstract: A Facile Synthesis of 2H‐Indazoles under Neat Conditions and Further Transformation into Aza‐γ‐Carboline Alkaloid Analogues in a Tandem One‐Pot Fashion.

AbstractAn efficient and green protocol for the microwave‐promoted synthesis of indazoles via a consecutive formation of C—N and N—N bonds without any catalyst and solvent is described.

ChemInform Abstract: Synthesis of Indazoles and Azaindazoles by Intramolecular Aerobic Oxidative C—N Coupling under Transition‐Metal‐Free Conditions.

AbstractIt offers a new, efficient, and environmentally friendly approach to a wide range of indazoles and azaindazoles.

Rhodium(III)-catalyzed N-nitroso-directed C-H addition to ethyl 2-oxoacetate for cycloaddition/fragmentation synthesis of indazoles.

Rh(III) -catalyzed N-nitroso-directed CH addition to ethyl 2-oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N-nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful CH functionalization-based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic-fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.

Synthesis of Indazoles and Azaindazoles by Intramolecular Aerobic Oxidative CN Coupling under Transition‐Metal‐Free Conditions

A transition-metal-free oxidative C-N coupling method has been developed for the synthesis of 1H-azaindazoles and 1H-indazoles from easily accessible hydrazones. The procedure uses TEMPO, a basic additive, and dioxygen gas as the terminal oxidant. This reaction demonstrates better reactivity, functional group tolerance, and broader scope than comparable metal catalyzed reactions.

Synthesis of indazole substituted-1,3,4-thiadiazoles and their anticonvulsant activity

ObjectivesTo synthesize a new series of indazole substituted-1,3,4-thiadiazole derivatives 7(a-l) and test the anticonvulsant activity against maximal electroshock (MES) seizure model in male Wistar rats. MethodsNew compounds were synthesized by the reaction of indazole substituted-1,3,4-thiadiazoles with various sulfonyl chlorides. The purity of the compounds was confirmed on the basis of their elemental analysis. Chemical structures of all the new compounds were established by 1H NMR and mass spectral data. Anticonvulsant study was done by MES seizure model and rotorod method was employed to determine the neurotoxicity. ResultsAll the compounds were synthesized in good yield. Out of twelve compounds, 7b and 7d are found to be most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). ConclusionsThe results obtained justify the usage of these compounds from their promising anticonvulsant activity. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the anticonvulsant activity and neurotoxicity of these compounds.

The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of Type 2 diabetes mellitus

Glucokinase activators represent a promising potential treatment for patients with Type 2 diabetes. Herein, we report the identification and optimization of a series of novel indazole and pyrazolopyridine based activators leading to the identification of 4-(6-(azetidine-1-carbonyl)-5-fluoropyridin-3-yloxy)-2-ethyl-N-(5-methylpyrazin-2-yl)-2H-indazole-6-carboxamide (42) as a potent activator with favorable preclinical pharmacokinetic properties and in vivo efficacy.

ChemInform Abstract: Stereoselective Synthesis of Indazole 2′-Deoxy-β-D- ribonucleosides: Glycosylation of the Nucleobase Anion.

The glycosylation of indazolyl anions derived from 4a, b with 2-deoxy-3,5-bis-O-(4-methylbenzoyl)-α-D-erythro-pentofuranosyl chloride (5) is described. The reaction was Stereoselective – exclusive β-D-anomer formation – but regioisomeric N1- and N2-(2′-deoxy-β-D-ribofuranosides) (i.e.6a and 7a, resp., and 6b and 7b, resp.) were formed in about equal amounts. They were deprotected to yield 8a, b and 9a, b. Compound 1, related to 2′-deoxyadenosine (3), and its regioisomer 2 were obtained from 8b and 9b, respectively, by catalytic hydrogenation. The anomeric configuration as well as the position of glycosylation were determined by 1D NOE-difference spectroscopy. The first protonation site of 1 and 2 was found to be the NH2 group. The N-glycosylic bond of 1H-indazole N1-(2′-deoxyribofuranosides) is more stable than that of the parent purine nucleosides. Compound 1 is no substrate for adenosine deaminase.

α-Enones in heterocyclic synthesis of indazole, thiazine, chromene and quinoline derivatives with their antimicrobial activities

α-Enones 1a,b react additively with hydrazine hydrate, thiourea, diethyl malonate, malononitrile, as well as ethyl cyanoacetate. Simultaneous cyclisation of the resulting 1:1 adducts yields indazole, thiazine, chromene and quinoline derivatives. The structures of all the synthesised compounds were confirmed by micro analytical and spectral data. The antimicrobial activity of some of the synthesised compounds were tested.

ChemInform Abstract: Synthesis of Indazoles by the [3 + 2] Cycloaddition of Diazo Compounds with Arynes and Subsequent Acyl Migration.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Indazoles by Cycloaddition of Diazo Acetates with Arynes

Synthesis of Indazoles by Cycloaddition of Diazo Acetates with Arynes

Synthesis of Indazoles by the [3+2] Cycloaddition of Diazo Compounds with Arynes and Subsequent Acyl Migration

The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively.

Synthesis of indazole- N-oxides via the 1,7-electrocyclization of azomethine ylides

The first examples of the 1,7-electrocyclization of azomethine ylides onto a nitro group, to give benz-1,2,6-oxadiazepine intermediates are reported. Subsequent ring contraction results in the formation of indazole- N-oxides.

Novel synthesis of indazoles from (η 6-arene)tricarbonylchromium complexes

Indazole chromium complexes and some of its derivatives were synthesised by two strategies: (1) by cyclisation of [η 6-2-(2′-phenylhydrazine)-1,3-dioxolane]tricarbonylchromium ( 2) in acidic conditions which was converted into σ-complex ( 11); (2) by thermolysis of Cr(CO) 6 with 1-bis(trimethylsilyl)methylindazole ( 3) and 2-bis(trimethylsilyl)methyl-3-trimethyl-silylindazole ( 4), using bulky protecting groups at N(1) or simultaneously at N(2) and C(3), to afford [η 6-1-bis(trimethylsilyl)methylindazole]tricarbonylchromium ( 14) and [η 6-2-bis(trimethylsilyl)methyl-3-trimethylsilylindazole]tricarbonylchromium ( 15), respectively. The deprotonation of complex 14 followed by electrophilic quench occurs at the C(4) and C(7) positions in a ratio of 3:1 and with complex 15 the deprotonation was completely regioselective at the C(7) position. The position of this substitution was confirmed by n.O.e. difference spectroscopy and X-ray crystal structure determination of the [η 6-2-bis(trimethylsilyl)methyl-7-methyl-3-trimethylsilylindazole]tricarbonylchromium ( 5). These complexes were decomplexed to produce new substituted indazole derivatives in good yield.