Synthesis
General procedure: To a dichloromethane/dioxane (V/V = 4/1) solution of isovaleraldehyde (1.721 g, 20 mmol) was slowly added dropwise a dichloromethane/dioxane (V/V = 4/1) solution of bromine (1.0 mL, 20 mmol). The reaction mixture was stirred at 10 °C to give 2-bromoisovaleraldehyde intermediate. Subsequently, 2-bromoisovaleraldehyde intermediate was slowly added dropwise to a dichloromethane/dioxane (30 mL) solution of thiourea (1.523 g, 20 mmol). Ethanol (6 mL) and triethylamine (2.424 g, 24 mmol) were added and the reaction was carried out at room temperature for 20 hours. Upon completion of the reaction, 100 mL of distilled water was added to the reaction mixture and the pH was adjusted to 12 with 12 N sodium hydroxide solution. after continued stirring for 1 h at room temperature, extraction was carried out with dichloromethane and water. The organic layer was washed with saturated brine and dried with anhydrous magnesium sulfate. Finally, the target compound 5-isopropylthiazol-2-amine was purified by silica gel column chromatography to give the target compound 5-isopropylthiazol-2-amine (1.202 g, 42.26% yield).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 22, p. 5521 - 5525
[2] European Journal of Medicinal Chemistry, 1999, vol. 34, # 10, p. 883 - 889
[3] Patent: WO2005/95367, 2005, A1. Location in patent: Page/Page column 28
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4119 - 4132
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4119 - 4132
