[Synthesis]
GENERAL STEPS: To a solution of N-(2-methoxy-6-methylphenyl)acetamide (9.28 g, 51.8 mmol) in ethyl acetate (100 mL) was added sequentially acetic anhydride (14.7 mL, 156 mmol), tetrabutylammonium bromide (0.84 g, 2.61 mmol), potassium acetate (10.16 g, 104 mmol), and isoamyl nitrite ( 9.1 mL, 67.7 mmol). The reaction mixture was heated to reflux for 9 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. To the residue, 6 N aqueous sodium hydroxide solution (100 mL) was added and stirred for 1 h at room temperature. Subsequently, the pH of the mixture was adjusted to 7-8 with 3 N hydrochloric acid and extracted with chloroform. The organic layers were combined, dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 3/1→1/1) to afford 7-methoxy-1H-indazole (3.95 g, 51% yield).1H-NMR (DMSO-d6) δ: 3.94 (3H, s), 6.82 (1H, d, J = 7.5 Hz), 7.02 (1H, dd, J = 8.0, 7.5 Hz), 7.30 (1H, d, J = 8.0 Hz), 8.01 (1H, d, J = 1.5 Hz), 13.27 (brs, 1H). |