Preparation method of key intermediate precursor and key intermediate of olbiquitrel

The preparation of key intermediates of obisetrix using a two-step reaction and a chiral phosphoric acid catalyst under mild conditions solves the problems of cumbersome steps and high cost in the existing technology, and achieves high yield and high economy in the preparation of key intermediates of obisetrix.

CN122127276APending Publication Date: 2026-06-02TAIZHOU UNIV
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Patent Information

Application Number
CN202512035492.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-12-31
Publication Date
2026-06-02

AI Technical Summary

Technical Problem

The existing methods for synthesizing the key intermediate (2R,4S)-2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydroquinoline-4-amine of obisetrium have problems such as complicated reaction steps, low raw material utilization, and high cost, especially the large amount of chiral phosphoric acid catalyst and harsh reaction conditions.

Method used

Using a small amount of chiral phosphoric acid catalyst, a two-step reaction is carried out in commercially available reagents to efficiently prepare the key intermediate of obisetrix via [4+2] cycloaddition and deprotection reactions, avoiding chiral resolution and using mild reaction conditions.

Benefits of technology

This study achieved high-yield and low-cost preparation of key intermediates of obisetri, simplified reaction steps, improved raw material utilization and economy, and has broad market application prospects.

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Abstract

The invention belongs to the technical field of organic synthesis, and relates to a preparation method of an olbiquitrel key intermediate precursor and a key intermediate. The method comprises the following steps: under the catalysis of chiral phosphoric acid, carrying out [4 + 2] cycloaddition reaction on 4-trifluoromethylaniline, propionaldehyde and N-vinylformamide, so as to highly enantioselectively obtain an olbiquitril key intermediate precursor N-((2R, 4S)-2-ethyl-6-trifluoromethyl-1, 2, 3, 4-tetrahydroquinoline-4-yl) formamide, and carrying out high-enantioselectivity reaction on the olbiquitril key intermediate precursor N-((2R, 4S)-2-ethyl-6-trifluoromethyl-1, 2, 3, 4-tetrahydroquinoline-4-yl) formamide. And then carrying out a deprotection reaction under an acidic condition to obtain the key intermediate of the orbiquitril. According to the method provided by the invention, the key intermediate (2R, 4S)-2-ethyl-6-trifluoromethyl-1, 2, 3, 4-tetrahydroquinoline-4-amine of the orbiquitril can be efficiently obtained only through two-step reaction by using a small amount of chiral catalyst and utilizing a reaction reagent which can be directly obtained commercially; under the mild condition that chiral resolution is not needed, the usability of the initial raw material is greatly improved, so that the yield of the target product and the step economy are greatly improved.
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