Abstract
A practical synthetic route of belinostat is reported. Belinostat was obtained via a five-step process starting from benzaldehyde and including addition reaction with sodium bisulfite, sulfochlorination with chlorosulfonic acid, sulfonamidation with aniline, Knoevenagel condensation, and the final amidation with hydroxylamine. Key to the strategy is the preparation of 3-formylbenzenesulfonyl chloride using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and acceptable overall yield. The scale-up experiment was carried out to provide 169 g of belinostat with 99.6% purity in 33% total yield.
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