General method: LiOH-H2O (1.5 eq.) was added in batches to a stirred solution of ester compounds 2a-2b (1.0 eq.) dissolved in THF (10 v/v) and H2O (10 v/v) at room temperature, and the reaction mixture was stirred continuously for 2 hr. The reaction progress was monitored by TLC. Upon completion of the reaction, THF was removed by concentration under reduced pressure, acidified to acidity with aqueous KHSO4, and subsequently extracted with a solvent mixture of 5% methanol and dichloromethane. The organic phases were combined, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the target solid products 3a-3b.
4.2.3 Synthesis of 2-(1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)acetic acid (3a): compound 2a (5 g, 18.78 mmol) was dissolved in 100 mL of THF:H2O (1:1) mixed solvent, LiOH-H2O (1.18 g, 28.18 mmol) was added, and the product was extracted as described in the The above general method was operated to give the white solid product 3a (4.1 g, 91% yield).1H NMR (400 MHz, DMSO-d6) δ: 13.27 (brs, 1H), 8.04 (s, 1H), 5.07 (s, 2H), 3.44 (s, 3H), 3.20 (s, 3H); m/z (ES)+: 239.04 [M +H]+.
