Example 402 Part A: To a solution of tetrahydrofuran (THF) (50 mL) of 6-bromoindazole (402A) (5.0 g, 25.4 mmol) was slowly added sodium hydride (95%, 672 mg, 26.6 mmol) under ice bath cooling conditions. The reaction mixture was stirred for 30 min. Subsequently, iodomethane (6.36 mL, 102 mmol) was added dropwise at room temperature. Upon completion of the reaction, the reaction was quenched with aqueous ammonium chloride and the organic and aqueous layers were separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: ethyl acetate/hexane gradient) afforded 1-methyl-6-bromoindazole (402B) (2.71 g, 51% yield) as a yellow oil and 2-methyl-6-bromoindazole (402C) (2.28 g, 43% yield) as a yellow crystalline solid, respectively. HPLC-MS analysis of 402B showed that the retention time t R = 1.69 min (UV 254 nm); calculated molecular weight C8H7BrN2 was 209.98, measured LCMS m/z 211.0 ([M + H]+). 402C was analyzed by HPLC-MS: retention time t R = 1.54 min (UV 254 nm); calculated molecular weight C8H7BrN2 was 209.98, measured LCMS m/z 211.0 ([M + H]+). 211.0 ([M + H]+).
