3389-01-3

Upstream product

• 3389-00-2 N–(2–(1H–pyrrol–1–yl)phenyl)benzamide 
• 6025-69-0 4-chloropyrrolo[1,2-a]quinoxaline 
• 98-80-6 phenylboronic acid 
• 6025-60-1 2-(1H-pyrrol-1-yl)aniline 
• 538-86-3 benzyl methyl ether 
• 98-88-4 benzoyl chloride 
• 88-74-4 2-nitro-aniline 
• 33265-60-0 1-(2-nitrophenyl)-1H-pyrrole 
• 100-46-9 benzylamine 
• 696-59-3 cis,trans-2,5-dimethoxytetrahydrofuran 
• 103-82-2 phenylacetic acid 
• 62-53-3 aniline 
• 350829-07-1 1-[2-isocyanophenyl]-1H-pyrrole 
• 1220282-44-9 N-benzyl-2-(1H-pyrrol-1-yl)aniline 

Downstream Products

• 203513-40-0 4-phenylpyrrolo[1,2-a]quinoxaline-1-carboxaldehyde 
• 203513-43-3 ethyl 4-methyl-3-(4'-phenylpyrrolo[1,2-a]quinoxalin-1'-yl)-1H-pyrrole-2-carboxylate 

Relevant academic research and scientific papers

Metal-Free C-H [5 + 1] Carbonylation of 2-Alkenyl/Pyrrolylanilines Using Dioxazolones as Carbonylating Reagents

A novel metal-free C-H [5 + 1] carbonylative annulation of 2-alkenyl/pyrrolylanilines with dioxazolones has been established for the assembly of the privileged quinolinones and pyrrolyl-fused quinoxalinones. Entirely differing from the existing reports, the dioxazolones herein behave with an innovative chemistry and first emerge as carbonylating reagents to participate in annulation reactions. Moreover, this process features exceedingly simple operation (only solvent) and tolerates both vinyl and aryl substrates. Comprehensive mechanistic studies indicate that the formed isocyanate intermediate plays a crucial role in enabling the carbonylation annulation.

Elemental Sulfur Mediated Synthesis of Pyrrolo[1,2- a ]quinoxalines from 1-(2-Nitroaryl)pyrroles

Methods to afford pyrrolo[1,2- a ]quinoxalines often require the use of prefunctionalized aniline precursors, transition metals, and/or harsh conditions. Herein we describe a simple coupling of 1-(2-nitroaryl)pyrroles and arylacetic acids, in the presence of elemental sulfur, to furnish the fused heterocycles in good yields. The conditions are compatible with many functionalities including ester, nitrile, halogen, and nitro groups. Use of benzyl alcohols and picoline coupling reagents was also attempted.

Synthesis of 4-Aryl Pyrrolo[1,2-α]quinoxalines via Iron-Catalyzed Oxidative Coupling from an Unactivated Methyl Arene

Herein, we describe the direct synthesis of pyrrolo[1,2-α]quinoxaline via oxidative coupling between methyl arene and 1-(2-aminophenyl) pyrroles. Oxidation of the benzylic carbon of the methyl arene was achieved by di-t-butyl peroxide in the presence of an iron catalyst, followed by conversion to an activated aldehyde in situ. Oxygen played a crucial role in the oxidation process to accelerate benzaldehyde formation. Subsequent Pictet-Spengler-type annulation completed the quinoxaline structure. The protocol tolerated various kinds of functional groups and provided 22 4-aryl pyrrolo[1,2-α]quinoxalines when various methyl arene derivatives were used. The developed method proceeded in air, and all catalysts, reagents, and solvents were easily accessible.

Catalyst-free synthesis of phenanthridinesviaelectrochemical coupling of 2-isocyanobiphenyls and amines

Catalyst free synthesis of 6-aryl phenanthridines and amides through an electrochemical reaction is reported in this study. The coupling reaction proceeds by the cathodic reduction ofin situformed diazonium ions, which are formed from anilines and an alkyl nitrite. The generated aryl radical diazonium ions coupled from isocyanides furnished the desired products in good yields. This cascade reaction was conducted in an undivided cell equipped with an RVC as the anode and Pt as the cathode usingnBu4NBF4as the electrolyte at room temperature. A series of detailed mechanistic studies have also been performed, including a radical clock experiment and cyclic voltammetry analysis.

Direct Synthesis of Pyrrolo[1,2-α]quinoxalines via Iron-Catalyzed Transfer Hydrogenation between 1-(2-Nitrophenyl)pyrroles and Alcohols

Herein, we describe novel iron-catalyzed transfer hydrogenation between alcohols and 1-(2-nitrophenyl)pyrroles for the synthesis of pyrrolo[1,2-α]quinoxalines. The tricarbonyl (η4-cyclopentadienone) iron complex catalyzed the oxidation of alcohols and the reduction of nitroarenes, and the corresponding aldehydes and aniline were generated in situ. The resulting Pictet-Spengler-type annulation/oxidation completed the quinoxaline structure formation. The protocol tolerated various kinds of functional groups and provided 29 samples of 4-substituted pyrrolo[1,2-α]quinoxalines. The developed method was also applied for the synthesis of additional polyheterocycles.

α-Hydroxy acid as an aldehyde surrogate: metal-free synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and other N-heterocyclesviadecarboxylative oxidative annulation reaction

A metal-free and efficient procedure for the synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and indolo[1,2-a]quinoxaline has been developed. The key features of our method include thein situgeneration of aldehyde from α-hydroxy acid in the presence of TBHP (tert-butyl hydrogen peroxide), and further condensation with various amines, followed by intramolecular cyclization and subsequent oxidation to afford the corresponding quinoxalines, quinazolinones derivatives in moderate to high yields.

KI-Mediated One-Pot Transition-Metal-Rree Synthesis of 4-Phenylpyrrolo[1,2-a]quinoxalines

An efficient and eco-friendly method for the synthesis of pyrrolo[1,2-a]quinoxalines is presented. Compared to previous methods, this protocol is transition-metal-free and only potassium iodide is required. A series of substituted 4-phenylpyrrolo[1,2-a]quinoxalines are obtained in moderate to good yields.

Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B

PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1–C4 and/or C7–C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index '40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.

Tin(ii) chloride dihydrate/choline chloride deep eutectic solvent: Redox properties in the fast synthesis of: N -arylacetamides and indolo(pyrrolo)[1,2- a] quinoxalines

In this contribution a physicochemical, IR and Raman characterization for the tin(ii) chloride dihydrate/choline chloride eutectic mixture is reported. The redox properties of this solvent were also studied by cyclic voltammetry finding that it can be successfully used as an electrochemical solvent for electrosynthesis and electroanalytical processes and does not require negative potentials as verified by the reduction of nitrobenzene. The potential use of this eutectic mixture as a redox solvent was further explored in obtaining aromatic amines and N-arylacetamides starting from a wide variety of nitroaromatic compounds. In addition, a fast synthetic strategy for the construction of a series of indolo(pyrrolo)[1,2-a]quinoxalines was developed by reacting 1-(2-nitrophenyl)-1H-indole(pyrrole) with aldehydes. This simple protocol offers a straightforward method for the construction of the target quinoxalines in short reaction times and high yields where the key step involves a tandem one-pot reductive cyclization-oxidation.

Synthesis of new piperazinyl-pyrrolo[1,2-: A] quinoxaline derivatives as inhibitors of Candida albicans multidrug transporters by a Buchwald-Hartwig cross-coupling reaction

Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald-Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of Candida albicans overexpressed in a Saccharomyces cerevisiae strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p. Further biological investigations were developed and for example, their antifungal potential was evaluated by measuring the growth of control yeast cells (AD1-8u-) and efflux pump-overexpressing cells (AD-CDR1 and AD-MDR1) after exposition to variable concentrations of the tested compounds. The MIC80 values of nineteen compounds ranging from 100 to 901 μM for AD-CDR1 demonstrated that relative resistance index (RI) values were between 8 and 274. In comparison, only seven compounds had RI values superior to 4 in cells overexpressing Mdr1p. These results indicated substrate behavior for nineteen compounds for CaCdr1p and seven compounds for CaMdr1p, as these compounds were transported via MDR transporter overexpressing cells and not by the AD1-8u- cells. Finally, in a combination assay with fluconazole, two compounds (1d and 1f) have shown a synergistic effect (fractional inhibitory concentration index (FICI) values ≤ 0.5) at micromolar concentrations in the AD-MDR1 yeast strain overexpressing CaMdr1p-protein, indicating an excellent potency toward chemosensitization.