21483-46-5

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 47, p. 140, 1982 DOI: 10.1021/jo00340a030

Upstream product

• 95-47-6 o-xylene 
• 6832-16-2 methyl diazoacetate 
• 108-38-3 m-xylene 
• 67-56-1 methanol 
• 37102-74-2 3-methylphthalic acid 
• 514-94-3 (R)-1,5,5,6-tetramethyl-cyclohexa-1,3-diene; (+)-α-pyronene 
• 762-42-5 dimethyl acetylenedicarboxylate 
• 186581-53-3 diazomethane 
• 15031-43-3 1,6-dimethylpyridin-2(1H)-one 
• 18064-04-5 dimethyl 1-methyl-7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate 
• 73245-20-2 dimethyl 1,3-dimethyl-3-hydroxy-2-oxobicyclo<2,2,2>octa-5,6-diene-dicarboxylate 
• 498-15-7 (+)-Δ³-carene 
• 1182669-71-1 N-(2-methylbenzoyl)-8-aminoquinoline 
• 933-88-0 ortho-toluoyl chloride 

Downstream Products

• 37102-74-2 3-methylphthalic acid 
• 72288-71-2 2-Carbomethoxy-3-methylbenzoesaeure 
• 24129-04-2 3-bromomethylphthalate dimethyl ester 

Relevant academic research and scientific papers

Regioselective arene homologation through rhenium-catalyzed deoxygenative aromatization of 7-oxabicyclo[2.2.1]hepta-2,5-dienes

Combined use of oxorhenium catalysts with triphenyl phosphite as an oxygen acceptor allowed efficient deoxygenative aromatization of oxabicyclic dienes. The reaction proceeded under neutral conditions and was compatible with various functional groups. Combining this deoxygenation with regioselective bromination and trapping of the generated aryne with furan resulted in benzannulative π-extension at the periphery of the PAHs. This enabled direct use of unfunctionalized PAHs for extension of π-conjugation. Iteration of the transformations increased the number of fused-benzene rings one at a time, which has the potential to alter the properties of PAHs by fine-tuning the degree of π-conjugation, shape, and edge topology.

Synthesis of phthalic acid derivatives: Via Pd-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates

A Pd(ii)-catalyzed alkoxycarbonylation of aromatic C-H bonds with alkyl chloroformates has been developed. A broad range of benzamides and alkyl chloroformates are compatible with this protocol. The reaction is operationally simple and scalable. The direct group could be readily removed to access substituted phthalic acid esters (PAEs), 1,2-dibenzyl alcohols and phthalamides. Besides alkoxycarbonylation of benzamide β-C-H bonds, γ-alkoxycarbonylation of 2-phenylacetamide is also feasible.

Design and optimization of aspartate N-acetyltransferase inhibitors for the potential treatment of Canavan disease

Canavan disease is a fatal neurological disorder caused by defects in the metabolism of N-acetyl-L-aspartate (NAA). Recent work has shown that the devastating symptoms of this disorder are correlated with the elevated levels of NAA observed in these patients, caused as a consequence of the inability of mutated forms of aspartoacylase to adequately catalyze its breakdown. The membrane-associated enzyme responsible for the synthesis of NAA, aspartate N-acetyltransferase (ANAT), has recently been purified and examined (Wang et al., Prot Expr Purif. 2016;119:11). With the availability, for the first time, of a stable and soluble form of ANAT we can now report the identification of initial inhibitors against this biosynthetic enzyme, obtained from the screening of several focused compound libraries. Two core structures of these moderate binding compounds have subsequently been optimized, with the most potent inhibitors in these series possessing sub-micromolar inhibition constants (Kivalues) against ANAT. Slowing the production of NAA via the inhibition of ANAT will lower the elevated levels of this metabolite and can potentially serve as a treatment option to moderate the symptoms of Canavan disease.

POTENT PHTHALATE INHIBITORS OF ASPARTATE N-ACETYLTRANSFERASE AND SELECTIVE ASPARTATE PATHWAY INHIBITORS

Phthalate derivatives that are aspartate-P-semialdehyde dehydrogenase (ASADH) inhibitor compounds, aspartate N-acetyltransferase (ANAT) inhibitor compounds, or both, are described, as well as methods of making the same, and methods of using the same.

Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors

Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is absent in mammals. Therefore, the key microbial enzymes involved in this pathway are attractive potential targets for development of new antibiotics with novel modes of action. The ASADH enzyme family shares the same substrate binding and active site catalytic groups; however, the enzymes from representative bacterial and fungal species show different inhibition patterns when previously screened against low molecular weight inhibitors identified from fragment library screening. In the present study several approaches, including fragment based drug discovery (FBDD), inhibitor docking, kinetic, and structure-activity relationship (SAR) studies have been used to guide ASADH inhibitor development. Elaboration of a core structure identified by FBDD has led to the synthesis of low micromolar inhibitors of the target enzyme, with high selectivity introduced between the Gram-negative and Gram-positive orthologs of ASADH. This new set of structures open a novel direction for the development of inhibitors against this validated drug-target enzyme.

7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: Design, synthesis, and biological activity

A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed.

N-METHYLAMINOMETHYL ISOINDOLE COMPOUNDS AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

This invention relates to N-methylaminomethyl-isoindoline compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.

Photochemical reactions of 1,3,3-trimethylbicyclo[2.2.2]octa-5,7-dien-2- ones

The photochemistry of 1,3,3-trimethylbicyclo[2.2.2]octa-5,7-dien-2-ones 1a-f containing multiple chromophoric moieties under various conditions is described. Upon direct irradiation, dienones 1a-f in benzene, acetonitrile, and methanol were found to aromatize through photoelimination of dimethylketene, which was trapped with 3-phenylprop-2-en-1-ol (12). Triplet sensitization of dienone 1a in acetone and in acetone/acetophenone mixed solvents afforded aromatic compound 2a, whilst bicyclic systems 1b-c were found to be unreactive on sensitization. In the cases of dienones 1d-f in acetone, aromatic compounds 2d-f and di-π-methane (DPM) photoproducts 3d-f and 4f were observed, but in the acetone/acetophenone mixed solvent system only DPM photoproducts were detected. Plausible mechanisms for these photochemical reactions are described. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Arene synthesis by extrusion reaction X. Synthesis of arenes by deoxygenation of endoxides with cyclopentadienyltitanium trichloride/lithium aluminum hydride and dicyclopentadienyltitanium dichloride/lithium aluminum hydride

The two homogeneous systems, cyclopentadienyltitanium trichloride/lithium aluminum hydride and dicyclopentadienyltitanium dichloride/lithium aluminum hydride have been utilized to deoxygenate 1,4-endoxides in tetrahydrofuran.The results show that they can provide corresponding arenes in fair yields.