- Preparation method of 2-methoxy-6-methylbenzoic acid
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The invention discloses a synthesis process of 2-methoxy-6-methylbenzoic acid, which comprises the following steps: (1) reduction hydrogenation reaction: by taking 2-methyl-6-nitrobenzoic acid or methyl 2-methyl-6-nitrobenzoate as a raw material, methanol as a solvent, hydrogen as a hydrogen source and palladium on carbon or platinum on carbon as a catalyst, carrying out hydrogenation reduction to prepare 2-amino-6-methylbenzoic acid or methyl 2-amino-6-methylbenzoate; (2) diazotization, hydrolysis and esterification one-pot reaction: by taking the reduction product as a raw material, and methanol as a solvent, performing diazotization, hydrolysis and esterification reaction under the action of a diazotization reagent to prepare methyl 2-hydroxy-6-methylbenzoate; (3) methylation reaction: with methyl 2-hydroxy-6-methylbenzoate as a raw material and dimethyl sulfate as a methylation reagent, carrying out methylation reaction in the presence of alkali to prepare methyl 2-methoxy-6-methylbenzoate; and (4) hydrolysis reaction: mixing the methyl 2-methoxy-6-methylbenzoate with alkali and water, conducting heating for hydrolysis, conducting cooling after the reaction is completed, adjusting the pH value to 1-3 by using acid, separating out a product, and conducting filtering and drying to obtain the 2-methoxy-6-methylbenzoic acid.
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Paragraph 0023-0024; 0029; 0033-0034; 0038-0039; 0045-0047
(2021/07/08)
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- COMPOUNDS MODULATING PROTEIN RECRUITMENT AND/OR DEGRADATION
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The invention provides cereblon binders for the degradation of proteins by the ubiquitin proteasome pathway for therapeutic applications.
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Paragraph 0444; 0445
(2021/06/26)
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- Copper-Catalyzed One-Pot Synthesis of Dibenzofurans, Xanthenes, and Xanthones from Cyclic Diphenyl Iodoniums
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Oxygenation of cyclic diphenyl iodoniums (CDPIs) with varied medium-ring sizes has been fully investigated. This practical copper-catalyzed tandem reaction of CDPIs with water as the oxygen source enables the construction of derivatised dibenzofurans and xanthenes at moderate to good yields. Moreover, structurally important xanthones are also successfully accessed under the oxygenation conditions with additional TEMPO.
- Zhu, Daqian,Li, Min,Wu, Zhouming,Du, Yongliang,Luo, Bingling,Huang, Peng,Wen, Shijun
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p. 4566 - 4571
(2019/07/09)
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- Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine
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One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.
- D'Hollander, Agathe C.A.,Westwood, Nicholas J.
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supporting information
p. 224 - 239
(2017/12/08)
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- HISTONE ACETYLTRANSFERASE ACTIVATORS AND COMPOSITIONS AND USES THEREOF
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The invention provides pharmaceutical compositions and methods for treating cancer, neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein by administering a HAT modulator and a HDAC modulator to a subject.
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- HISTONE ACETYLTRANSFERASE ACTIVATORS AND USES THEREOF
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The invention provides compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.
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- Metabolically stable dibenzo[ b, e ]oxepin-11(6 H)-ones as highly selective p38 MAP kinase inhibitors: Optimizing anti-cytokine activity in human whole blood
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Five series of metabolically stable disubstituted dibenzo[b,e]oxepin-11(6H) -ones were synthesized and tested in a p38α enzyme assay for their inhibition of tumor necrosis factor-α (TNF-α) release in human whole blood. Compared to the monosubstituted dibenzo[b,e]oxepin-11(6H)-one derivatives, it has been shown that the additional introduction of hydrophilic residues at position 9 leads to a substantial improvement of the inhibitory potency and metabolic stability. Using protein X-ray crystallography, the binding mode of the disubstituted dibenzoxepinones and the induction of a glyince flip in the hinge region were confirmed. The most potent compound of this series, 32e, shows an outstanding biological activity on isolated p38α, with an IC50 value of 1.6 nM, extraordinary selectivity (by a factor >1000, Kinase WholePanelProfiler), and low ATP competitiveness. The ability to inhibit the release of TNF-α from human whole blood was optimized down to an IC50 value of 125 nM. With the promising dibenzoxepinone inhibitor 3i, a pharmacokinetic study in mice was conducted.
- Baur, Benjamin,Storch, Kirsten,Martz, Kathrin E.,Goettert, Marcia I.,Richters, André,Rauh, Daniel,Laufer, Stefan A.
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p. 8561 - 8578
(2013/12/04)
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- Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity
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A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat.
- Ruchelman, Alexander L.,Man, Hon-Wah,Zhang, Weihong,Chen, Roger,Capone, Lori,Kang, Jian,Parton, Anastasia,Corral, Laura,Schafer, Peter H.,Babusis, Darius,Moghaddam, Mehran F.,Tang, Yang,Shirley, Michael A.,Muller, George W.
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p. 360 - 365
(2013/02/23)
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- Synthesis of (+)-varitriol analogues via novel and versatile building blocks based on julia olefination
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The synthesis of (+)-varitriol (1) analogues was achieved through, the use of Julia olefination. The potential anticancer properties of 1 coupled with, our interest in developing building blocks that enable olefin formation under the Julia protocol constitute the basis of our research project. Efforts are aimed at the synthesis of building blocks 2 and 3 and to explore their use towards the synthesis of (+)-varit:riol analogues. Herein, we would, like to present the synthesis of building block 3 and its ability to react with variety of substituted aromatic-, heterocyclic- and carbohydrate-derived aldehydes to yield alkene 6 in moderate to good yields with E as the major isomer. The successful, coupling of 2 with (furanoside moieties) aldehydes 5k, 5m and 5n in particular and the obtainment of compound 23 reflect the promise associated with the new strategy.
- Senthilmnrugan, Annamalai,Aidhen, Indrapal Singh
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scheme or table
p. 555 - 564
(2010/04/24)
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- Titanocene(III) chloride mediated radical-induced synthesis of 3,4-dihydroisocoumarins: synthesis of (±)-hydrangenol, (±)-phyllodulcin, (±)-macrophyllol and (±)-thunberginol G
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A radical-promoted synthesis of 3,4-dihydroisocoumarins has been achieved in moderate to good yields using titanocene(III) chloride (Cp2TiCl) as the radical initiator. The total synthesis of four naturally occurring dihydrocoumarins hydrangenol, phyllodulcin, macrophyllol and thunberginol G has been accomplished using the radical technology. Cp2TiCl was prepared in situ from commercially available titanocene dichloride (Cp2TiCl2) and Zn-dust in THF under argon.
- Mandal, Samir Kumar,Roy, Subhas Chandra
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experimental part
p. 11050 - 11057
(2009/04/11)
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- Synthesis of Saturated Anacardic Acids, and Alkenyl and Alkynyl Analogues
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The C-alkylation of esters of 2-methoxy-6-methylbenzoic acid and of the 4-methyl isomers affords a route to homologous compounds including in the former case members of the natural anacardic acids from Anacardium occidentale and ω-alkynyl compounds suitable for synthesising other natural phenolic lipids or for structure/activity studies.
- Tyman, John H. P.,Visani, Naina
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p. 228 - 240
(2007/10/03)
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- A New Synthetic Route to 4-Bromo-7-methoxyphthalide and 3-Hydroxy-7-methoxyphthalide from 2-Methoxy-6-methylbenzoate Side Chain and Nuclear Bromination
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Ethyl 2-methoxy-6-methylbenzoate was converted via its acid and acid chloride, into the methyl ester.Bromination of the methyl and ethyl esters with the halogen in carbon tetrachloride at reflux in the presence of light resulted in both side-chain and nuc
- Islam, Md. Rabiul,Joule, John A.
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p. 367 - 378
(2007/10/02)
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- REGIOSELECTIVE METALLATIONS OF (METHOXYMETHOXY)ARENES
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The methoxymethoxy substituent when attached to an aromatic ring functions as a moderately strong ortho-directing group in hydrogen-metal exchenge reactions.In many cases the propensity of the methoxymethoxylated arene toward ring metallations is greatly enhanced with concomitant suppression of undesirable side reactions such as nucleophilic attack and addition of metallating species.Unlike many other ortho-directing groups, the regio-direction of the methoxymethoxy substituent when in conjunction with other weaker directing groups is dependent upon the metallating medium.Thus, by changing the electron donating capacity of the metallating medium it is possible to selectively direct metallation to either of the positions ortho to the methoxymethoxy substituent.
- Ronald, Robert C.,Winkle, Mark R.
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p. 2031 - 2042
(2007/10/02)
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