2-(Dimethylaminomethyl)-4-(2-aminoethylthiomethyl)thiazole

156-57-0

140176-73-4

78441-62-0

General procedure for the synthesis of 2-(dimethylaminomethyl)-4-(2-aminoethylthiomethyl)thiazole from 2-mercaptoethylamine hydrochloride and 1,4-chloromethyl-2-dimethylaminothiazole hydrochloride: 2-aminoethanol hydrochloride (cysteamine hydrochloride, 520 g, 4.5 mol) was suspended in water (500 mL). This suspension was cooled to 5 °C and sodium hydroxide solution (45% w/w, 870 mL; 14.7 mol) was slowly added at 5-10 °C. Subsequently, hydroxylamine sulfate (100 g; 0.6 mol) was added to this suspension with continuous stirring. Another solution was prepared by dissolving 4-chloromethyl-2-dimethylaminomethylthiazole hydrochloride (1000 g; 4.43 mol) in water (1250 mL). The solution was slowly added to the above suspension while keeping the temperature below 10 °C and the reaction was continued at 10 °C for 1 hour. The reaction process was confirmed by qualitative HPLC monitoring. Upon completion of the reaction, the reaction mixture was diluted with water (2000 mL), heated to 40-45°C and extracted with toluene (2 x 2000 mL). The toluene extracts were combined and treated with activated charcoal at 40-45 °C for 30 min. The treated solution was filtered through a HYFLO bed to remove the activated carbon and the filtrate was evaporated at 60 °C under reduced pressure to remove toluene, resulting in 910 g of the target product in 88% yield.