465529-57-1

68-12-2

872607-89-1

1. 2.0 M tetrahydrofuran solution of n-butylmagnesium chloride (3.05 mL) was added to toluene (20 mL) under nitrogen protection and cooled to -10 °C. 2. 1.6 M hexane solution of n-butyllithium (7.63 mL) was slowly added to the above solution, keeping the reaction mixture stirred at -10 °C for 1 hour. 3. The reaction mixture was further cooled to -30 °C, then a tetrahydrofuran solution (10 mL) of 5-bromo-1-methyl-1H-indazole (2.35 g) was added. 4. The reaction mixture was slowly warmed to -10 °C and stirring was continued at this temperature for 1 hour. 5. N,N-dimethylformamide (5 mL) was added and the reaction was kept stirring at -10 °C for 1 hour. 6. the reaction was quenched with 2 N hydrochloric acid (20 mL) and the reaction mixture was allowed to warm slowly to room temperature. 7. After 30 minutes, the reaction mixture was alkalized with saturated aqueous sodium bicarbonate and then extracted with ethyl acetate (2 x 80 mL). 8. The organic phases were combined and washed sequentially with saturated sodium bicarbonate solution (2 x 100 mL), 10% aqueous lithium chloride solution (2 x 100 mL) and brine. 9. The organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. 10. The residue was purified by column chromatography on silica gel (120 g silica gel, eluent 10-30% ethyl acetate in cyclohexane solution). 11. The fractions containing the target product were combined and concentrated under reduced pressure to give 1-methyl-1H-indazole-5-carbaldehyde (1.43 g, 80% yield) as a white solid. 12. HPLC analysis: retention time Rt = 2.2 min (gradient 1); MS analysis: m/z [M + H]+ = 161 (gradient 1).