a) Synthesis of 4-bromo-1-ethyl-1H-pyrazole: To a DMF solution of 4-bromo-1H-pyrazole (5 g, 34 mmol) was added potassium carbonate (K2CO3, 11.75 g, 85.03 mmol, 2.5 equiv) and ethyl iodide (8 g, 51 mmol, 1.5 equiv). The reaction mixture was stirred at room temperature for 12 hours. Upon completion of the reaction, a quench and extraction operation was performed as in Intermediate Example 5(c). The solvent was removed by distillation and the crude product obtained was purified by column chromatography (60-120 mesh silica gel, 40% ethyl acetate in hexane solution as eluent), resulting in the target product 1-ethyl-4-bromopyrazole in 84% (5 g) yield. The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6) and LC-MS (ESI): 1H NMR (300 MHz, DMSO-d6) δ 8.02 (s, 1H), 7.55 (s, 1H), 4.15 (q, 2H), 1.37 (t, 3H); LC-MS (ESI): calculated mass: 175.03; Measured mass: 177.0 [M + H]+ (retention time: 0.56 min).
