14080-51-4

General procedure for the synthesis of 2-aminothiophene-3-amides from 1,4-dithio-2,5-diol and cyanoacetamide: Triethylamine (36 mL, 256 mmol) was added to a solution of ethanol (400 mL) containing 2-cyanoacetamide (10.8 g, 128 mmol) and 1,4-dithiazan-2,5-diol (19.5 g, 128 mmol). The reaction mixture was stirred at room temperature for 5 minutes and then heated to reflux for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, filtered and concentrated in vacuum. The residue was dissolved in ethyl acetate (400 mL) and washed sequentially with 1 M aqueous sodium hydroxide (200 mL), water (2 x 200 mL) and brine (200 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 2-aminothiophene-3-amide (16 g, 113 mmol, 88% yield) as a light yellow solid.LC-MS [M+H]+ m/z 143.

[1] Patent: WO2003/104218, 2003, A1. Location in patent: Page 13
[2] Synthesis (Germany), 2013, vol. 45, # 1, p. 45 - 52
[3] Patent: WO2012/30894, 2012, A1. Location in patent: Page/Page column 87
[4] Tetrahedron Letters, 2007, vol. 48, # 30, p. 5261 - 5264
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 19, p. 6734 - 6750