p-Toluenesulfonic acid → 5-(2,6-Dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine

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Reaction Steps

A mixture of 10 g (59.2 mmol) of 4-amino-2-methylthiopyrimidine-5-carboxaldehyde, 9.7 g (59.9 mmol) of 2,6-dichloroaniline and 1 g (5.3 mmol) of 4-toluenesulfonic acid in 200 ml of xylene was heated at reflux with the azeotropic removal of water for 24 hours. The mixture was cooled and evaporated. 50 ml of acetic acid and 20 ml of toluene were added to the residue. The mixture was cooled in ice and treated portionwise over 30 minutes with 5 g (147 mmol) of sodium borohydride. After 1 hour the mixture was evaporated and the residue was stirred in a mixture of 100 ml of ethyl acetate and 100 ml of 2M aqueous sodium hydroxide for 1 hour. The phases were separated and the organic phase was dried over magnesium sulfate, filtered and evaporated. Crystallisation of the residue from aqueous ethanol gave 2.4 g (13%) of 5-(2,6-dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine as a white solid. The mother liquors were evaporated and flash chromatography of the residue on silica gel using diethyl ether/hexane (1:1) for the elution gave a further 2.1 g (11%) of 5-(2,6-dichlorophenyl)aminomethyl-4-amino-2-methylthiopyrimidine as a white solid.

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