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Synthesis 2016; 48(18): 3120-3126
DOI: 10.1055/s-0035-1561865
paper
© Georg Thieme Verlag Stuttgart · New York

A New and Practical Synthesis of Cariprazine through the Facile Construction of 2-[trans-4-(3,3-Dimethylureido)cyclohexyl]acetic Acid

Xiaowen Chen
a   School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, P. R. of China   Email: leifu@sjtu.edu.cn
b   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry,285 Gebaini Rd, Shanghai 201203, P. R. of China   Email: li.jianqi@sipi.com.cn
,
Feng Ni
b   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry,285 Gebaini Rd, Shanghai 201203, P. R. of China   Email: li.jianqi@sipi.com.cn
,
Yu Liu
b   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry,285 Gebaini Rd, Shanghai 201203, P. R. of China   Email: li.jianqi@sipi.com.cn
,
Lei Fu*
a   School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Rd, Shanghai 200240, P. R. of China   Email: leifu@sjtu.edu.cn
,
Jianqi Li*
b   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry,285 Gebaini Rd, Shanghai 201203, P. R. of China   Email: li.jianqi@sipi.com.cn
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Further Information

Publication History

Received: 20 March 2016

Accepted after revision: 25 April 2016

Publication Date:
23 June 2016 (online)

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Abstract

A new, practical, and improved synthetic route to cariprazine is described. The key step is the facile preparation of 2-[4-(3,3-dimethylureido)cyclohexyl]acetic acid in the trans configuration through direct recrystallization. The entire synthetic procedure was accomplished under mild conditions while avoiding tedious purification processes. The trans configuration of cariprazine was confirmed by X-ray crystallographic analysis.

Key words

cariprazine - antipsychotic agents - synthetic methods - recrystallization - trans configuration - X-ray crystallography

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561865.
  • Supporting Information
 

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