18740-38-0

1189-71-5

4651-81-4

18740-38-0

Methyl 2-aminothiophene-3-carboxylate (95 g) and dichloromethane (2.85 L) were added to a 5 L reaction flask fitted with a mechanical stirrer, an internal temperature probe, and a nitrogen bubbler, and the mixture was cooled to -60 °C. Chlorosulfonyl isocyanate (89.81 g) was slowly added while maintaining the internal temperature at -60°C to -55°C. After addition, the reaction mixture was allowed to gradually warm up to room temperature. The reaction was monitored by LC/MS until the feedstock was completely consumed. The reaction mixture was concentrated to dryness under vacuum and the solid residue was transferred to a 5L reaction flask with water (1.8L). The mixture was heated at 75 °C for 1 h and then cooled to 30 °C. Subsequently, 10M NaOH aqueous solution (200mL) was added and the mixture was heated at 85°C for 20 minutes and then cooled to room temperature. The mixture was acidified to pH=1 with concentrated hydrochloric acid and stirred at room temperature for 18 hours, during which time a precipitate formed. The solid was collected by vacuum filtration and the filter cake was washed with water (3 x 300 mL). The solid was dried in a vacuum oven at 55 °C for 24 h to afford thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione as an off-white solid (80.05 g, 78.8% yield).1H NMR (400 MHz, DMSO-d6) δ 7.083 (d, J=5.6 Hz, 1H), δ 7.124 (d, J=5.6 Hz , 1H); LCMS (ESI pos) m/e 169 (M+1).