17480-07-8

Usage

Chemical class

Isoindole derivatives

Physical form

Yellow to brown powder

Molecular weight

261.27 g/mol

Uses

Synthesis of pharmaceuticals, agrochemicals, and as a building block for complex organic molecules

Potential applications

Materials science, organic electronics

Unique properties

Structural and electronic properties

Upstream product

• 136918-14-4 phthalimide 
• 21040-45-9 Cinnamyl acetate 
• 1883-19-8 vinyltri-n-butylphosphonium bromide 
• 100-52-7 benzaldehyde 
• 4407-36-7 (2E)-3-phenyl-2-propen-1-ol 
• 1074-82-4 potassium phtalimide 
• 4392-24-9 Cinnamyl bromide 
• 4335-61-9 2-[(Z)-3-phenylprop-2-enyl]-2,3-dihydro-1H-isoindole-1,3-dione 
• 5428-09-1 3-phthalimido-1-propene 
• 591-50-4 iodobenzene 
• 108-86-1 bromobenzene 
• 3485-84-5 N-vinylphthalimide 
• 100-44-7 benzyl chloride 
• 2687-12-9 cinnamyl chloride 

Downstream Products

• 1579955-77-3 N-cinnamyl-2-cyanoacetamide 
• 1152032-92-2 2-(E)-cinnamyl-3-(difluoro(phenylsulfanyl)methyl)-3-hydroxyisoindolin-1-one 
• 4335-60-8 (E)-cinnamylamine 
• 54981-86-1 2-(3-phenylpropyl)-1H-isoindole-1,3(2H)-dione 
• 65472-88-0 naftifine 
• 62624-46-8 (S)-(+)-3-phenylpyrrolidine 
• 5435-02-9 4-methyl-N-(3-phenylpropyl)benzenesulfonamide 

Relevant academic research and scientific papers

Hypolipidemic activity of phthalimide derivatives. IV: Further chemical modification and investigation of the hypolipidemic activity of N-substituted imides

A further investigation of N-substituted derivatives of phthalimide for hypolipidemic activity has revealed that the chain length, as well as the type of substitution on the N-alkyl chain of phthalimide is critical for biological activity. In these studies the hypolipidemic activity was not improved by extending the chain length beyond five carbon atoms in the alkyl and alkanoic acid series. Imido nitrogen substitutents, other than alkanoic acids, methyl ketones, and alkyl groups, caused a reduction in hypolipidemic activity, e.g., hydroxy, amino, hydroxymethyl, or carbethoxy. Reduction of the keto group in the side chain to an alcohol, as well as forming derivatives of the keto group, did not improve the hypolipidemic activity with the exception of 1-N-phthalimidobutan-3-one semicarbazone. This compound demonstrated improved hypocholesterolemic activity over phthalimide and 1-N-phthalimidobutan-3-one. Substitution of the 3-position of the aromatic moiety of phthalimide with an amino or nitro group, as well as substituting a pyridine or cyclohexyl ring for the phenyl ring, led to the loss of hypolipidemic activity.

Sulfinates from Amines: A Radical Approach to Alkyl Sulfonyl Derivatives via Donor-Acceptor Activation of Pyridinium Salts

Synthetically versatile alkyl sulfinates can be prepared from readily available amines, using Katritzky pyridinium salt intermediates. In a catalyst-free procedure, primary, secondary, and benzylic alkyl radicals are generated by photoinduced or thermally induced single-electron transfer (SET) from an electron donor-acceptor (EDA) complex, and trapped by SO2 to generate sulfonyl radicals. Hydrogen atom transfer (HAT) from Hantzsch ester gives alkyl sulfinate products, which are used to prepare a selection of medicinal chemistry relevant sulfonyl-containing motifs.

PROTEIN LABELLING

A process for labelling a target protein, such as a target enzyme, such as a deubiquitinating enzyme (DUB). The process comprises providing a probe-protein complex comprising a probe and the target protein. The probe comprises a recognition element and a

Tuning the Selectivity of Palladium Catalysts for Hydroformylation and Semihydrogenation of Alkynes: Experimental and Mechanistic Studies

Here, we describe a selective palladium catalyst system for chemodivergent functionalization of alkynes with syngas. In the presence of an advanced ligand L2 bearing 2-pyridyl substituent as a built-in base, either hydroformylation or semihydrogenation of diverse alkynes occurs with high chemo- and stereoselectivity under comparable conditions. Mechanistic studies, including density functional theory (DFT) calculations, kinetic analysis, and control experiments, revealed that the strength and concentration of acidic cocatalysts play a decisive role in controlling the chemoselectivity. DFT studies disclosed that ligand L2 not only promotes heterolytic activation of hydrogen similar to frustrated Lewis pair (FLP) systems in the hydrogenolysis step for hydroformylation but also suppresses CO coordination to promote semihydrogenation under strong acid conditions. This switchable selectivity provides a strategy to design new catalysts for desired products.

Mechanochemical Oxidative Heck Coupling of Activated and Unactivated Alkenes: A Chemo-, Regio- and Stereo-Controlled Synthesis of Alkenylbenzenes

In this work, we present an efficient mechanochemical strategy for chemo-, regio- and stereo-selective oxidative Heck coupling of readily accessible arylboron reagents/heteroaromatics with cyclic and acyclic olefins. Mono- and bis-arylation were achieved without the need of ligands, directing groups or prefunctionalized alkenes, and the reaction chemo-selectivity could be controlled by tuning of the oxidative system. This protocol offers the synthesis of alkenylbenzenes in broad substrate scope, satisfactory yields and excellent selectivity even in the gram scale. (Figure presented.).

Structural Basis for Achieving GSK-3β Inhibition with High Potency, Selectivity, and Brain Exposure for Positron Emission Tomography Imaging and Drug Discovery

Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, and brain-penetrant oxazole-4-carboxamide-based inhibitors of glycogen synthase kinase-3 (GSK-3). An isotopologue of our first-generation lead, [3H]PF-367, demonstrates selective and specific target engagement in vitro, irrespective of the activation state. We discovered substantial ubiquitous GSK-3-specific radioligand binding in Tg2576 Alzheimer's disease (AD), suggesting application for these compounds in AD diagnosis and identified [11C]OCM-44 as our lead GSK-3 radiotracer, with optimized brain uptake by PET imaging in nonhuman primates. GSK-3β-isozyme selectivity was assessed to reveal OCM-51, the most potent (IC50 = 0.030 nM) and selective (>10-fold GSK-3β/GSK-3α) GSK-3β inhibitor known to date. Inhibition of CRMP2T514 and tau phosphorylation, as well as favorable therapeutic window against WNT/β-catenin signaling activation, was observed in cells.

Highly chemoselective, sterically sensitive NHC-catalysed amine acylation with pyridil

A new strategy for the protection of amines has been developed involving reaction with pyridil under the influence of N-heterocyclic carbene catalysis. The methodology is capable of distinguishing between two amines characterised by small differences in steric bulk and the resulting pyridoyl amides can be cleaved without requiring either strongly acidic or basic hydrolysis.

Catalytic Diastereo- and Enantioselective Fluoroamination of Alkenes

The stereoselective synthesis of syn-β-fluoroaziridine building blocks via chiral aryl iodide-catalyzed fluorination of allylic amines is reported. The method employs HF-pyridine as a nucleophilic fluoride source together with mCPBA as a stoichiometric oxidant, and affords access to arylethylamine derivatives featuring fluorine-containing stereocenters in high diastereo- and enantioselectivity. Catalyst-controlled diastereoselectivity in the fluorination of chiral allylic amines enabled the preparation of highly enantioenriched 1,3-difluoro-2-amines bearing three contiguous stereocenters. The enantioselective catalytic method was applied successfully to other classes of multifunctional alkene substrates to afford anti-β-fluoropyrrolidines, as well as a variety of 1,2-oxyfluorinated products.

Photo-induced Decarboxylative Heck-Type Coupling of Unactivated Aliphatic Acids and Terminal Alkenes in the Absence of Sacrificial Hydrogen Acceptors

1,2-Disubstituted alkenes such as vinyl arenes, vinyl silanes, and vinyl boronates are among the most versatile building blocks that can be found in every sector of chemical science. We herein report a noble-metal-free method of accessing such olefins through a photo-induced decarboxylative Heck-type coupling using alkyl carboxylic acids, one of the most ubiquitous building blocks, as the feedstocks. This transformation was achieved in the absence of external oxidants through the synergistic combination of an organo photo-redox catalyst and a cobaloxime catalyst, with H2 and CO2 as the only byproducts. Both control experiments and DFT calculations supported a radical-based mechanism, which eventually led to the development of a selective three-component coupling of aliphatic carboxylic acids, acrylates, and vinyl arenes. More than 90 olefins across a wide range of functionalities were effectively synthesized with this simple protocol.

Direct use of allylic alcohols and allylic amines in palladium-catalyzed allylic amination

Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields. Furthermore, this methodology can be easily applied to the one-step synthesis of two drugs, cinnarizine and naftifine, on a gram scale.