Hydrochloric Acid → 5-(2-Methylsulphonylaminomethylpropan-2-yl)-2-(2-methoxy-4-methylmercaptophenyl)-benzimidazole

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Reaction Steps

Air is passed into a solution of 13 g. of 4-(2-acetamidomethylprop-2-yl)-1,2-diaminobenzene (obtained in Example 1f) and 18 g. of the bisulphite adduct of 2-methoxy-4-methylmercaptobenzaldehyde in 500 ml. methanol for 8 hours at ambient temperature. The reaction mixture is then evaporated and the residue purified by column chromatography (1.5 liters silica gel; trichloromethane:methanol:glacial acetic acid 10:1:0.2 v/v/v). There are obtained 16 g. 5-(2-acetamidomethylpropan-2-yl)-2-yl)-2-(2-methoxy-4-methylmercaptophenyl)-benzimidazole in the form of a brownish viscous mass which is boiled under reflux in 400 ml. ethanol and 100 ml. concentrated hydrochloric acid for 3 days. The reaction mixture is then evaporated and the residue is rendered alkaline with 2N aqueous sodium hydroxide solution and extracted with dichloromethane. The product is purified by column chromatography (silica gel; dichloromethane/methanolic ammonia 10:1 v/v) to give 5.4 g. 5-(2-aminomethylpropan-2-yl)-2-(2-methoxy-4-methylmercaptophenyl)-benzimidazole in the form of a brownish viscous mass, as well as 1 g. of unreacted starting material. 2.7 g. of the product are mesylated analogously to Example 33 to give 3.1 g. of the title compound in the form of a dihydrate; m.p 237°-239° C.

Provenance & Evidence