Synthesis
Step 1: Synthesis of ethyl 5-amino-1,3,4-thiadiazole-2-carboxylate
Hydrazinothioformamide (10 g, 54.8 mmol) was dissolved in phosphorus trichloride (25 mL) followed by addition of ethyl 2-chloro-2-oxoacetate (6.1 mL, 54.8 mmol). The reaction mixture was heated to 70 °C and stirred continuously for 5 hours. Upon completion of the reaction, phosphorous trichloride was completely evaporated under reduced pressure. The residue was diluted with ice water (150 mL) and the pH was adjusted with saturated sodium bicarbonate solution to 8. Subsequently, the mixture was extracted with ethyl acetate (200 mL). The organic layer was separated, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by fast column chromatography (silica gel 100-200 mesh, eluent 2% methanol/dichloromethane) to afford ethyl 5-amino-1,3,4-thiadiazole-2-carboxylate as a yellow solid (3.1 g, 24% yield).
1H NMR (400 MHz, DMSO-d6) δ: 7.94 (s, 2H), 4.29 (q, 2H), 1.27 (t, 3H); LC-MS m/z calculated value [M + H]+ 174.03, measured value 174.1.
References
[1] Patent: WO2013/49565, 2013, A1. Location in patent: Page/Page column 68
[2] Annali di Chimica (Rome, Italy), 1959, vol. 49, p. 2124,2131
[3] Patent: WO2007/38865, 2007, A1. Location in patent: Page/Page column 47
