The general procedure for the synthesis of 5-bromo-2-ethyl-4-pyrimidinecarboxylic acid from 3,4-dibromo-5-hydroxyfuran-2(5H)-one and propionamidine hydrochloride was as follows: first, sodium ethanolate solution was prepared by slowly adding sodium (356 mg, 15.5 mmol) to ethanol (5.9 mL). The freshly prepared sodium ethanol solution (3.5 mL) was added to a stirred suspension of propionamidine hydrochloride (1.05 g, 9.69 mmol). After heating the mixture to 55 °C, the heating bath was removed to maintain a constant temperature and an ethanol solution of 3,4-dibromo-5-hydroxyfuran-2(5H)-one (1 g, 3.87 mmol) was added slowly and dropwise, followed by the addition of sodium ethanol solution (2 mL). After completion of the reaction, the mixture was cooled, filtered and evaporated to dryness. The residue was vigorously shaken with hydrochloric acid (2 x 2.4 mL). The brown precipitate was collected by filtration, washed with cold water and subsequently freeze-dried to give 5-bromo-2-ethylpyrimidine-4-carboxylic acid (330 mg, 37% yield) as a yellow solid. The product was analyzed by LCMS showing a molecular ion peak of 231 [M + 1]+ and the 1H NMR (400 MHz, DMSO-d6) data were as follows: δ 1.25 (t, J = 7.6 Hz, 3H), 2.88 (q, J = 7.6 Hz, 2H), 9.05 (s, 1H).
