Synthesis
The general procedure for the synthesis of 5-chloro-3-methyl-1,2,4-thiadiazole from acetamidine hydrochloride and perchloromethylmercaptan was as follows: to a stirred mixture of acetamidine hydrochloride (38.1 g, 0.40 mol) and trichloromethanesulfonyl chloride (75 g, 0.40 mol) at ±5°C, an aqueous solution containing NaOH (75.7 g, 0.40 mol) was slowly added dropwise (126mL). After the dropwise addition, the reaction mixture was stirred at 0°C for 30 minutes and then allowed to warm up to room temperature. After completion of the reaction, the mixture was filtered and the layers were separated. The aqueous phase was extracted with dichloromethane (3 x 150 mL). All organic phases were combined and washed with brine (2 x 150 mL) and subsequently dried with anhydrous magnesium sulfate. Finally, the solvent was removed under reduced pressure to afford the target product 5-chloro-3-methyl-1,2,4-thiadiazole (43 g, 83% yield) as a dark colored oil.
References
[1] Patent: US2010/160392, 2010, A1. Location in patent: Page/Page column 18
[2] Patent: WO2007/100670, 2007, A1. Location in patent: Page/Page column 48
[3] Patent: WO2005/7636, 2005, A1. Location in patent: Page/Page column 14; 15
[4] Journal of Medicinal Chemistry, 2002, vol. 45, # 9, p. 1887 - 1900
[5] Chemische Berichte, 1957, vol. 90, p. 182,186
