合成路线1

Two new related ways for the synthesis of cariporide mesylate have been reported: 1) The reaction of 4-isopropylbenzoic acid (I) with chlorosulfonic acid gives 3-(chlorosulfonyl)-4-isopropylbenzoic acid (II), which is reduced wth sodium sulfite/NaOH to the sorresponding sulfinic acid (III). The methylation of (III) with methyl iodide/NaOH in dimethylacetamide affords 4-isopropyl-3-(methanesulfonyl)benzoic acid methyl ester (IV), which is finally condensed with gunidine (V). 2) The hydrolysis of benzoate (IV) with NaOH in methanol/water gives the corresponding free acid (VI), which is then condensed with guanidine (V) by means of dicyclohexylcarbodiimide (DCC) in THF. 3) Benzoic ester (IV) can also be obtained by alkylation of 4-bromo-3-(methanesulfonyl)benzoic acid methyl ester with isopropylmagnesium chloride by means of CuI, ZnCl2 and a PdCl2 catalyst in THF.