Preparation method for trans 4-amino-cyclohexyl acetate derivative

Abstract

The invention provides a preparation method for a trans 4-amino-cyclohexyl acetate derivative. The preparation method comprises the following steps that a formula (please see the description for the formula) is provided, wherein R is methyl or ethyl; a compound III is prepared from the raw materials of 4-amino cyclohexanone II and is subjected to hydrogenation reduction, a compound I crude product is obtained, acid is added, and salt is formed; and a compound I is prepared by adding alkali. According to the preparation method, 4-amino cyclohexanone not protected by amino is adopted as raw materials, witting reaction is conducted, and then through catalytic hydrogenation, the trans crude product of the preparation method is obtained. The crude product can be subjected to salifying crystallization so as to obtain the purer trans product, and the trans:syn ratio is 95-99.9:5-0.1. The product compound is high in purity and can be used for preparing cariprazine. Operation is simple, the raw materials are easy to obtain, industrial production is suitable, and large application value is achieved.

Description

technical field

[0001] The invention relates to medicinal chemistry, in particular to a preparation method of a drug intermediate, in particular to a preparation method of trans 4-amino-cyclohexyl ethyl ester derivatives. Background technique

[0002] Cariprazine (Cariprazine) was jointly developed by Gedeon Richter Ltd and Forest Laboratories. It was first reported that it has a dopamine D3 / D2 partial agonist, and has the characteristics of preferentially binding D3R and DA partial agonists. It is used for the treatment of schizophrenia, Mania, severe depression, expected to be launched in the United States in 2015 as an anti-schizophrenia drug, its chemical name is trans-1-{4-[2-[4-(2,3-dichlorophenyl)- Piperazin-1-yl]-ethyl]-cyclohexyl}-3,3-dimethylurea hydrochloride. Its structural formula is as follows:

[0003]

[0004] Patent (CN1829703) discloses the preparation method of cariprazine. Use piperazine compound 1 and amino-protected 4-aminocyclohexyl acetaldehyde ...

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