16233-51-5

22288-78-4

16233-51-5

The general procedure for the synthesis of thieno[3,2-d]pyrimidine-2,4-dione from methyl 3-amino-2-thiophenecarboxylate was as follows: to a mixed solution containing methyl 3-amino-2-thiophenecarboxylate (101) (100.0 g, 636.9 mmol, 1.0 eq.), acetic acid (705 mL), and water (600 mL) was added slowly over a period of 1 h. To a mixture containing methyl 3-aminothiophene-2-carboxylate (101) ( 154.8 g, 1.91 mol, 3.0 eq.) of an aqueous solution (326 mL). The reaction mixture was stirred at room temperature for 20 hours before being filtered and the filter cake was washed with deionized water (500 mL). The resulting solid was transferred to an appropriately sized reactor, 2M aqueous sodium hydroxide solution (1.65 L) was added and the slurry was stirred for 2 h. The formation of the target product, thieno[3,2-d]pyrimidine-2,4-dione, was confirmed by LCMS. Subsequently, the reaction mixture was cooled to 10 °C and the pH was adjusted to 5.0-6.0 by slow addition of 3M aqueous hydrochloric acid (1.29 L). The slurry was filtered, the solids were washed with deionized water (700 mL) and dried in a vacuum oven at 50 °C for 24 h. Compound 102 (100 g, 94% yield) was obtained as an off-white solid. lCMS (m/z): 169.1 [ M + H]+. 1H NMR (400MHz, DMSO-d6): δ 6.92 (d, J=5.2Hz, 1H), 8.04 (d, J=5.2Hz, 1H), 11.14 (s, 1H), 11.51 (s, 1H).