Synthetic route of tucatinib

Tucatinib is chemically synthesized through the chemical synthesis of sodium benzoate, which is the raw material of tucatinib. The corresponding benzoate is obtained through an esterification reaction between sodium benzoate and the corresponding sulfate ester. The purpose is to introduce the methyl benzoate required for the reaction, and then react with benzoic acid. The compound required for the methyl ester activation reaction is dissolved in a suitable solvent and reacts with methyl benzoate and the conditional compound to obtain the tucatinib intermediate. The phosphate ester group in the intermediate is removed through a dephosphorylation reaction to obtain the final tucatinib product. The preparation process is very tedious and requires a variety of special compounds and intermediates. In addition, multiple steps in the manufacturing process require special conditions such as high temperature, high pressure, and inert gas protection.