合成路线1

Cariporide has been obtained by two similar ways: 1) The oxidation of 4-isopropylbenzaldehyde (I) with sodium perborate in hot acetic acid gives 4-isopropylbenzoic acid (II), which is sulfonated with hot chlorosufonic acid yielding 3-(chlorosulfonyl)-4-isopropylbenzoic acid (III). The reduction of (III) with sodium sulfite in hot NaOH solution affords 4-isopropyl-3-sulfinobenzoic acid (IV), which is alkylated with methyl bromide and NaOH in DMF giving 4-isopropyl-3-(methylsulfonyl)benzoic acid (V). The reaction of (V) with SOCl2 in refluxing toluene yields 4-isopropyl-3-(methylsulfonyl)benzoyl chloride (VI), which is finally condensed with guanidine (VII) in DMF. 2) The iodination of 4-isopropylbenzoic acid (II) with iodine chloride or N-iodosuccinimide (NIS) gives 3-iodo-4-isopropylbenzoic acid (VIII), which is treated first with SOCl2 to afford the corresponding acyl chloride (IX), and then with methanol yielding 4-iodo-4-isopropylbenzoic methyl ester (X). The reaction of (X) with sodium methylsulfite (XI) gives 4-isopropyl-3-(methylsulfonyl)benzoic acid methyl ester (XII), which is finally treated with guanidine (VII) in refluxing THF.