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Synthesis 2015; 47(20): 3133-3138
DOI: 10.1055/s-0035-1560471
DOI: 10.1055/s-0035-1560471
psp
New Synthetic Process for Bosutinib
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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