Preparation method of 3-amino-4-methylmercapto maleimide compound

Abstract

The invention relates to a preparation method of a 3-amino-4-methylmercapto maleimide compound, which comprises the following steps: in an organic solvent, under the condition of oxygen, by using methylmercapto Bunte salt, secondary amine and N-methylmaleimide as reaction raw materials, carrying out a cascade reaction catalyzed by transition metal copper to obtain the 3-amino-4-methylmercapto maleimide compound. The method is simple in reaction condition and high in product yield and purity, opens up a synthetic route and method for preparation of the 3-amino-4-methylmercapto maleimide compound, and has good application potential and research values.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a preparation method of 3-amino-4-methylmercaptomaleimide compound. Background technique [0002] 3,4-Difunctionalized maleimide as the core skeleton widely exists in marine natural alkaloids and anti-tumor active molecules with important biological activities, candidate drug molecules and AIE fluorescent materials, such as: G2 cell cycle checkpoint kinase Isogranulatimide, LPS-induced macrophage inhibitor Himanimide A, anti-breast cancer drug Camphorataimide B, specific porcupine inhibitor, marine alkaloid aqabamycin G, and liver X receptor agonist GSK3987. In addition, maleimide can also undergo a variety of functional group transformations to synthesize derivatives such as succinimide, tetrahydropyrrole and 2-pyrrolone. Therefore, exploring the efficient construction of 3,4-difunctionalized maleimides from cheap and readily available raw materia...

AI Technical Summary

Problems solved by technology

[0005] Because compounds containing maleimide structures are so important, medicinal chemists have conducted a lot of research on the modification and synthesis of their parent structures, however, only a few cases of 3-mercapto-4-aminomaleimide derivatives have been reported so far The synthetic method of: In 2002, Dubinina, G.G. et al reported (Reactions of 3,4-dichloromaleimides with N-andS-nucleophiles, Ukrainskii Khimicheskii Zhurnal, 68,47-51; 2002), using 3,4-dichloromaleimides The 3-amino-4-arylmercaptomaleimide compound is obtained by reflux of arylamine, arylamine and thiophenol under the condition of triethylamine, but the reaction requires expensive 3,4-dichloromaleimide Amines as raw materials, even using foul-smelling thiophenols are likely to cause environmental pollution

In 2018, Professor Zhao Shengyin of Donghua University and others reported (Three-Component Coupling Reactions of Maleimides, Thiols, and Amines: One-Step Construction of 3,4-Heteroatom-functionalized Maleimides by Copper-Catalyzed C(sp2)-H Thioamination , Advanced Synthesis & Catalysis, 2018, 360, 173-179;), using transition metal copper / oxygen to catalyze the three-component cascade reaction of maleimide, arylamine and thiophenol to realize 3-amino-4-arylmercaptomaleimide The preparation of imine target compound, the use of malodorous thiophenol is easy to cause environmental pollution

In 2020, our research group also reported the synthesis of 3-amino-4-methylmercaptomaleimide compound (Copper -Catalyzed Oxidative Thioamination of Maleimides with Amines and Bunte Salts, Organic Letters 2020, 22, 5, 1863-1867), however, the reaction conditions can only be applied to special structures when investigating methylmercapto Bunte salt as a thiomethylation reaction Secondary amine compounds, lack of a simple, efficient, universally applicable catalytic system for series of secondary amine compounds

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