99171-11-6

61296-22-8

5188-07-8

99171-11-6

6.1 Synthesis of 5-(methylthio)-1,3-thiazol-2-amine (512) A solution was prepared by dissolving sodium methanethiol (1.09 g, 14.8 mmol) in methanol (18.0 mL). The solution was added dropwise to a suspension of 2-amino-5-bromothiazole monohydrobromide 505 (2.50 g, 14.0 mmol) in anhydrous ethanol (18.0 mL) over 5 min. The reaction mixture gradually became homogeneous. Subsequently, another solution of sodium methanethiol (1.09 g, 14.8 mmol) in methanol (12.0 mL) was added to the reaction system. The reaction system was slowly heated to 45 °C and maintained at this temperature for 40 min, then the heating was stopped and the reaction mixture was allowed to stir at room temperature overnight. The progress of the reaction was monitored by thin layer chromatography (unfolding agent ratio 1:1 ethyl acetate/hexane) to confirm that the raw materials were almost consumed and new products were generated. Sodium methanethiol (0.20 g, 2.85 mmol) was added to the reaction system and heated to 50 °C again. After 2 hours of continuous heating, the reaction mixture was cooled to room temperature and concentrated under reduced pressure. The concentrated residue was dissolved in dichloromethane, washed sequentially three times with water and once with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the target product 512 (1.12 g, 55% yield) as an orange solid. The NMR hydrogen spectrum data of the product 512 were as follows: 1H-NMR (400 MHz, DMSO-d6) δ 7.20 (s, 2H), 6.97 (s, 1H), 2.29 (s, 3H) ppm.