A method for preparing fully substituted amidines

Abstract

The invention discloses a method for preparing total substitution amidine. Sulfonamide derivatives, nitrile derivatives and diazo derivatives are used as reaction substrates, transition metal is usedas a catalyst, and four-component cascade reaction is carried out in organic solvents to prepare the total substitution amidine. The method has the advantages that the reaction is economical, the substrates are high in universality, functionalization in late periods can be facilitated, raw material waste can be prevented, reaction conditions are mild, the method can be implemented in air and is low in catalyst dosage and favorable for product purification and large-scale industrial application, and after-treatment is simple and convenient; raw materials such as reactants and the catalyst for the total substitution amidine are inexpensive and easily available, the reaction is reasonable in composition, ligands can be omitted, the method is high in atom economy, includes few reaction steps,is high in yield only by the aid of the one-step reaction, conforms to modern green chemistry and medicinal chemistry requirements and directions, is suitable for screening high-activity amidines medicines and is suitable for large-scale industrial production, and gram-scale reaction can be effectively carried out.

Description

technical field [0001] The invention relates to a method for preparing fully substituted amidines, belonging to the technical field of organic synthesis. Background technique [0002] Fully substituted amidines are ubiquitous in natural products and play important roles in the pharmaceutical and agrochemical industries. Furthermore, fully substituted amidines are often considered privileged scaffolds in medicinal chemistry for the discovery and optimization of new synthetic drug molecules. Fully substituted amidines are also synthetic building blocks for the construction of various heterocyclic compounds. At present, the methods for preparing fully substituted amidines have disadvantages such as harsh reaction conditions, cumbersome preparation of raw materials, large amount of raw materials, expensive raw materials, and narrow substrate scope. For example: [0003] (1) Yasumaru Hatanaka et al. reported the method of preparing fully substituted amidines by the condensatio...

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Problems solved by technology

[0003] (1) Yasumaru Hatanaka et al. reported the method of preparing fully substituted amidines by the condensation of sulfonyl azide and thioamide, but the sulfonyl azide and thioamide raw materials in this reaction usually require one or more steps of reaction to pre-prepare , resulting in a narrow range of substrates and high preparation costs (see: Yasumaru Hatanaka; Chem. Commun. 2013, 49 ,10242−10244);

[0004] (2) Sukbok Chang et al. reported the three-component reaction of terminal alkynes, sulfonyl azides and amines to prepare fully substituted amidines, but this reaction can only prepare N -Alkyl-substituted amidines, and the reaction requires the use of toxic sulfonyl azides (see: Sukbok Chang; J. Am. Chem. Soc . 2005, 127 , 2038−2039);

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