Citation: Xiangguo Meng, Siju Bi, Shixin Jin, Kai Wu, Shanchao Wu, Lei Shao, Pierre-Antoine Bonnet, Chunquan Sheng. A novel route for the synthesis of androgen receptor antagonist enzalutamide[J]. Chinese Chemical Letters, ;2023, 34(6): 108096. doi: 10.1016/j.cclet.2022.108096 shu

A novel route for the synthesis of androgen receptor antagonist enzalutamide

Xiangguo Meng ^a ,
Siju Bi ^{a, c} ,
Shixin Jin ^c ,
Kai Wu ^a ,
Shanchao Wu ^b ,
Lei Shao ^{a, *,} ,
Pierre-Antoine Bonnet ^{d, *,} ,
Chunquan Sheng ^{b, *,}

a.
College of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China
b.
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
c.
State Key Lab of Anti-Infectives, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China
d.
IBMM, Faculty of Pharmacy, Montpellier University, CNRS, ENSCM, 34093 Montpellier Cedex 5, France

shaol@sumhs.edu.cn

pierreantoine.bonnet1@umontpellier.fr

shengcq@smmu.edu.cn

Received Date: 14 September 2022
Revised Date: 20 December 2022
Accepted Date: 22 December 2022
Available Online: 24 December 2022

Figures(6)

A novel route of enzalutamide was developed in five steps. Starting from 4-amino-2-(trifluoromethyl)benzonitrile (7) and Boc-2-aminoisobutyric acid (16), condensation, deprotection, Ullmann coupling, cyclization and amination provided enzalutamide in 41.0% total yield. This route avoids the using of toxic chemical, unstable intermediate and high-risk reaction. It is a potential efficient and economical procedure for industrialization.
- Enzalutamide,
- Condensation,
- Deprotection,
- Ullmann coupling,
- Cyclization,
- Amination
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