General procedure for the synthesis of 5-methoxy-1H-indazole using 2-methyl-4-methoxyaniline as starting material: aqueous (8.1 ml) solution of sodium nitrite (3.38 g, 49.0 mmol) was slowly added dropwise to acetic acid (350 ml) solution of 4-methoxy-2-methylaniline (6.69 g, 48.8 mmol) under ice-water bath conditions. The temperature was strictly controlled not to exceed 25°C during the reaction, followed by continuous stirring at room temperature overnight. After completion of the reaction, the reaction mixture was poured into water and extracted with chloroform. The organic layers were combined, washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent ratio of chloroform/methanol=9/1) to give 5-methoxy-1H-indazole (1.30 g, 18% yield). The product was characterized by 1H-NMR (DMSO-d6) and the chemical shifts δ were 3.76 (3H, s), 6.98 (1H, dd, J=8.8,1.8 Hz), 7.15 (1H, d, J=1.8 Hz), 7.42 (1H, d, J=8.8 Hz), 7.93 (1H, s), and 12.89 (1H, brs).
