Synthesis 2015; 47(20): 3133-3138
DOI: 10.1055/s-0035-1560471
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© Georg Thieme Verlag Stuttgart · New York

New Synthetic Process for Bosutinib

Yongjun Mao*
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
,
Chunping Zhu
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
,
Ziyang Kong
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
,
Jiao Wang
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
,
Guoqing Zhu
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
,
Xinfeng Ren
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 23 July 2015

Accepted after revision: 17 August 2015

Publication Date:
09 September 2015 (online)


Abstract

A new and improved synthetic route to bosutinib is described on a hectogram scale. The key step is the intramolecular cyclization of a 3-(2-aminophenyl)-3-oxopropanenitrile with N,N-dimethylformamide dimethyl acetal to form the 3-cyano-4-hydroxyquinoline ring of 7-(3-chloropropoxy)-6-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile. A practical synthetic method to 2,4-dichloro-5-methoxyaniline is also established. Bosutinib is obtained in 18.0% yield over nine steps from acetovanillone with 98.9% purity (HPLC).

 
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