合成路线1

As shown in Scheme 22540502a, initially, starting material (I) is converted to benzothiazol (II) by treatment of sodium thiocyanate in the presence of bromine. Alkali hydrolysis of compound (II) gives thiol (III), which is immediatly submitted to S-alkylation with 1-bromo-2-chloroethane, followed by acid esterification, which gives thioether (IV). After protection of the amino group of compound (IV) with tosyl chloride, treatment of NaOH affords benzothiazine ester (V), and next hydrolysis produces the key intermediate (VI). Subsequently, compound (VI) is converted to the corresponding acid chloride and amidated with dimethyl homoglutamate to give the amide (VII). The tosyl group of the amide (VII) is removed with HBr-AcOH to give the amine (VIII), which is effectively alkilated with 6-(bromomethyl)-,4-diaminopteridine (IX) to produce (X). Finally, compound (X) is hydrolyzed with 1N NaOH to yield MX-68.