60758-86-3Relevant articles and documents
New synthesis process for 3-methoxyl-4-ethoxybenzonitrile
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Paragraph 0026; 0029; 0032; 0035, (2017/09/01)
The invention discloses a new synthesis process for 3-methoxyl-4-ethoxybenzonitrile, and relates to the technical field of organic synthesis. The new synthesis process for the 3-methoxyl-4-ethoxybenzonitrile comprises the following steps: taking ethyl vanillin as a raw material, taking N,N-dimethylformamide as a solvent, reacting the raw material and the solvent with potassium carbonate at first to form potassium salt, and reacting the obtained potassium salt with methyl iodide to obtain 3-methoxyl-4-ethoxy-benzaldehyde as an intermediate; adding hydroxylamine hydrochloride in a formic acid solution of the 3-methoxyl-4-ethoxy-benzaldehyde as the intermediate, heating and dehydrating, and carrying out desolventizing and recrystallization to obtain the high-purity 3-methoxyl-4-ethoxybenzonitrile finished product. The ethyl vanillin which is low in cost and is easily obtained as the raw material, aftertreatment operation is simple, and after being recycled, the N,N-dimethylformamide as the solvent can be directly used for other items; the 3-methoxyl-4-ethoxy-benzaldehyde as the intermediate are used for next reaction when not purified, so that purification cost is saved, and yield loss is avoided; and moreover, solid wastes are not produced in the whole process, and the total yield reaches 93.8%.
Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase
Xiong, Yan,Li, Fengling,Babault, Nicolas,Dong, Aiping,Zeng, Hong,Wu, Hong,Chen, Xin,Arrowsmith, Cheryl H.,Brown, Peter J.,Liu, Jing,Vedadi, Masoud,Jin, Jian
, p. 1876 - 1891 (2017/03/17)
G9a-like protein (GLP) and G9a are highly homologous protein lysine methyltransferases (PKMTs) sharing approximately 80% sequence identity in their catalytic domains. GLP and G9a form a heterodimer complex and catalyze mono- and dimethylation of histone H3 lysine 9 and nonhistone substrates. Although they are closely related, GLP and G9a possess distinct physiological and pathophysiological functions. Thus, GLP or G9a selective small-molecule inhibitors are useful tools to dissect their distinct biological functions. We previously reported potent and selective G9a/GLP dual inhibitors including UNC0638 and UNC0642. Here we report the discovery of potent and selective GLP inhibitors including 4 (MS0124) and 18 (MS012), which are >30-fold and 140-fold selective for GLP over G9a and other methyltransferases, respectively. The cocrystal structures of GLP and G9a in the complex with either 4 or 18 displayed virtually identical binding modes and interactions, highlighting the challenges in structure-based design of selective inhibitors for either enzyme.
Preparation method of Apremilast
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Paragraph 0057; 0058, (2016/11/28)
The invention relates to a preparation method of Apremilast, comprising the following steps: by taking 3-hydroxy-4-methoxybenzaldehyde as a staring material, reacting with hydroxylamine hydrochloride to obtain 3-hydroxy-4-methoxy cyanobenzene, reacting with bromoethane to obtain 3-ethyoxyl-4-methoxy cyanobenzene, and then reacting with dimethyl sulfone under the action of n-butyllithium, and hydrolyzing in aqueous hydrochloric acid solution to obtain 1-(3-ethyoxyl-4-methoxyphenyl)-2-(mesyl)ketol); finally by taking S-(-)-alpha, alpha-diphenyl-2-pyrrolidine methanol as a chiral catalyst and taking borane dimethyl sulfide complex solution as a reductant, obtaining chirality S-3-ethyoxyl-4-methoxy group-alpha[(mesyl)benzyl alcohol], and then reacting with 3-acetamido-phthalimide under the action of triphenylphosphine and diethyl azodicarboxylate, thus obtaining the Apremilast. According to the preparation method, the process is effectively simplified, the reaction conditions are mild, the product yield and purity are relatively high, and large-scale industrial production is benefited.
