Chiral beta-arylamine compounds prepared by asymmetric reductive amination reaction and preparation method of chiral beta-arylamine compounds

Abstract

The invention relates to chiral beta-arylamine compounds prepared by asymmetric reductive amination reaction and a preparation method of the chiral beta-arylamine compounds. The chiral beta-arylamine compounds are prepared by hydrogenised asymmetric reductive amination reaction under the action of chiral catalysts on the basis of alpha-aryl ketone and aminodiphenylmethane. By the synthesis method, catalyst consumption can be reduced to 5*10<-5>, enantioselectivity of products is up to 98%, and a diaryl methyl group can be removed from N-diaryl methyl-beta-arylamine obtained from the reaction under mild conditions to finally obtain first-grade beta-arylamine, so that the problem of synthesis of the chiral beta-arylamine compounds is solved. In addition, since relevant raw materials are very cheap, the chiral beta-arylamine compounds and the preparation method have extremely high industrial application potential.

Description

technical field [0001] The invention relates to chiral amine compounds, in particular to a chiral β-arylamine compound prepared by asymmetric reductive amination reaction and a method thereof. Background technique [0002] β-Arylamines are the pharmacophore of many important drugs. For example, the British Shire’s drugs Vyvanse and AdderallXR for the treatment of neurological diseases, the British AstraZeneca Pharmaceuticals Co., Ltd.’s asthma drug Symbicort, the US Bristol-Myers Squibb Pharmaceuticals Co., Ltd.’s AIDS drug Reyataz, and the US AbbVie Pharmaceuticals Co., Ltd. for the treatment of AIDS. The drug Norvir of Japan and the drug Flomax of Japan Astellas Pharmaceutical Co., Ltd. for the treatment of benign prostatic hyperplasia, their main pharmacophore is chiral β-arylamine. Therefore, it is of great significance to study and develop the reactions for the preparation of chiral β-arylamines. [0003] Asymmetric reductive amination is a green and efficient method ...

AI Technical Summary

Problems solved by technology

So far, the development of asymmetric reductive amination is relatively slow, and there are no industrial examples, mainly due to the high cost caused by the low yield of the reaction, the difficulty of chiral control and the low catalytic efficiency of the catalyst.

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