Triethylamine → Ethyl 4-((3-chloro-4-methoxybenzyl)amino)-2-(methylsulfanyl)pyrimidine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

(1)-b) To a stirred suspension of 2-methylthio-4-chloro-5-ethoxycarbonylpyrimidine (145.0 g, 0.62 mol) and (3-chloro-4-methoxyphenyl)methylamine (129.0 g, 0.62 mol) in dimethylformamide (435 ml) is added triethylamine (131.8 g, 1.30 mol) below 20° C. The mixture is stirred at the same temperature for about an hour. After the completion of the reaction, ethyl acetate (1450 ml) and water (870 ml) are added to the reaction mixture and stirred. The organic layer is separated and washed with water (870 ml) and a solution of sodium chloride (72.5 g) in water (290 ml), and dried over anhydrous magnesium sulfate (29.0 g). After removal of the drying agent by filtration and washed with ethyl acetate (145 ml), the filtrate and washings are combined and concentrated under reduced pressure. The resultant solid is suspended in 2-propanol (145 ml) and the mixture is concentrated under reduced pressure. The resultant solid is dissolved in hot 2-propanol (1450 ml) and the solution is seeded with 2-methylthio-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine crystals at 55° C. The mixture is cooled down to 45-50° C. and continuously stirred at the same temperature for more than an hour. Then the mixture is cooled down below 10° C. and continuously stirred for more than 30 minutes. The precipated crystals are collected by filtration, washed with 2-propanol (145 ml) and dried at 50° C. for about 16 hours to produce 2-methylthio-5-ethoxycarbonyl-4-(3-chloro-4-methoxybenzylamino)pyrimidine (209.2 g, 91%). mp. 86-88° C.

Provenance & Evidence