Process for synthesizing effective azolylamine derivative

Abstract

The invention relates to a method of using the close-ring reaction of cyclopropane which is induced by the thermal rearrangement of methylene cyclopropyl aldehyde and hydrazide or hydrazine hydrate after the open-ring for synthesizing 2, 3-dibasic pyrrole amine derivatives. No matter substituents in substrates of the methylene cyclopropane aldehyde are aromatic rings with various withdrawing electron or donating electron groups or various alkyls and hydrogen for the substitution of various functional groups in the reaction, the reaction can be carried out successfully. And corresponding pyrrole amine derivatives can be obtained at the yield from medium to perfect. In the reaction, the substrates with pyrrole amine skeletons are generated and are proved to be provided with various perfect biological activities and pharmacological activities in previous researches. Simultaneously, the compounds have perfect modification characteristics. Especially in the synthesis of the pyrrole amine compounds without any protecting group, free amino groups with potential application value can realize various functional-group transformations conveniently. No catalysts and additives are required to be added in the reaction. Therefore, the method is environment-friendly, and products can be purified easily. The reaction can well satisfy the requirement of preparing compounds with high purity in medical chemistry.

Description

technical field [0001] The invention relates to a new method for synthesizing pyrrolamine derivatives by using cyclopropane ring-opening induced by thermal rearrangement of methylene cyclopropanal and hydrazide or hydrazine hydrate and then ring-closing. Background technique [0002] The chemical and physical properties of organic heterocyclic compounds are different from ordinary carbocyclic compounds due to the electronegativity of heteroatoms and the influence of the lone pair of electrons, and most of them are N-heterocyclic compounds. N-heterocyclic compounds widely exist in the fields of medicinal chemistry, materials chemistry and organic synthesis chemistry. Compounds with pyrrolamine structure (see figure below) generally have good [0003] [0004] Among them, R 1 -R 5 For various substituents or hydrogen atoms [0005] Biological activity and a wide range of medicinal value, many pyrrolamine derivatives with simple or complex substituents have been proved t...

AI Technical Summary

Problems solved by technology

However, the Paal-Knorr condensation reaction has relatively large limitations in the synthesis of pyrrole amine compounds without protective groups in the amine group, that is, when hydrazine hydrate is used to react with 1,4-dicarbonyl compounds, the reaction yield It is often relatively low, and is accompanied by the generation of pyrrole or dihydropyridazine compounds with the occurrence of side reactions, which makes it difficult to purify the target product

If the reaction is carried out with protected hydrazine, a further step of deprotection is required to obtain the pyrrolamine compound with free amine groups, which makes the large-scale process production more expensive

In addition, pyrrolamine compounds can also be generated from exocyclic azolium ylides and other substrates, but more steps are required, and the value in the synthetic industry is not great [(a) Butler, R.N.; Cloonan, M.O.; Smith , G.M. ARKIVOC, 2003, vii, 244-254. (b) Batanero, B.; Elinson, M.N.; Barba, F. Tetrahedron 2004, 60, 10787]

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