1111638-74-4

956722-10-4

1111638-74-4

Preparation of 4-(5-Iodo-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine (A): a solution of NaNO2 (20.0 g, 0.29 mol) in water (150 mL) was slowly added to a mixture of 4-[2-(methylthio)pyrimidin-4-yl]-1H- pyrazol-5-amine (50.0 g, 0.24 mol) to a mixed solution of glacial acetic acid (400 mL) and water (100 mL), keeping the reaction temperature between -3°C and -1°C. Subsequently, concentrated H2SO4 (10 mL) was added to the reaction system and a solution of potassium iodide (120.0 g, 1.2 mol) and I2 (123.0 g, 0.48 mol) in water (200 mL) was added slowly and dropwise. The reaction mixture was heated to 50°C and maintained for 2 hours. Upon completion of the reaction, the reaction solution was neutralized with ammonia and excess iodine was treated with Na2S2O3 solution. The precipitate was collected by filtration and the filtrate was extracted with ethyl acetate. The organic layers were combined, concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: THF:EtOAc = 4:1) to afford 4-(5-iodo-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine (A) (42.2 g, 54.6%) as a yellow solid.1H NMR (400 MHz, DMSO-d6): δ 8.55 (d, 1H), 8.35 (s, 1H), 7.55 (d, 1H), 2.55 (s, 3H).