To a mixture of methyl 4-bromo-1H-pyrazole-3-carboxylate (15.0 g, 73.2 mmol) and Cs2CO3 (59.6 g, 182.9 mmol) in DMF (150 mL) was added slowly and dropwise at 0 °C under nitrogen protection iodomethane (14.7 mL, 236.0 mmol). The reaction mixture was stirred at 25 °C for 16 hours. After completion of the reaction, the mixture was filtered and the filter cake was washed with ethyl acetate (200 mL x 2). The combined filtrates were washed with water (70 mL x 4) and the aqueous phase was then back-extracted with ethyl acetate (150 mL). All organic phases were combined, dried with Na2SO4, filtered and concentrated to dryness under reduced pressure. The crude product was purified by fast column chromatography (gradient elution: petroleum ether/ethyl acetate from 100/0 to 50/50) to afford methyl 4-bromo-1-methyl-1H-pyrazole-3-carboxylate (240a, 8.3 g, 51.8% yield) and methyl 4-bromo-1-methyl-1H-pyrazole-5-carboxylate (240b, 7.0 g, 43.7% yield), both as white solid . 1H NMR (400 MHz, CDCl3) data for compound 240a: δ 7.48 (s, 1H), 4.15 (s, 3H), 3.93 (s, 3H). m/z (M + H) + 219.0 in MS (ESI).
