Methyl iodide → 5-(difluoromethoxy)-3-iodo-1-methyl-1H-indazole

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To a solution of 5-(difluoromethoxy)-3-iodo-1H-indazole (562 mg, 1.81 mmol) in THF (10.00 mL) at 0° C. was added KOtBu (1M in THF, 2.54 mL, 2.54 mmol) and the mixture stirred at 0° C. for 30 min then MeI (360 mg, 159 μL, 2.54 mmol) added. The reaction mixture was stirred at 0° C. for 30 min then warmed to 25° C. and stirred for 1.5 h. The reaction mixture was quenched with saturated ammonium chloride in water and extracted with dichloromethane (3×30 mL), organics dried over MgSO4 and concentrated to a clear oil. Purification by chromatography (80 g column, 50 μm from Analogix, 0-20% EtOAc in hexanes over 20 min) gave 5-(difluoromethoxy)-3-iodo-1-methyl-1H-indazole (465 mg, 1.43 mmol, 79.2%) as a waxy off-white solid. MS (M+H)+=324.9; 1H NMR (CDCl3) δ: 7.32-7.40 (m, 1H), 7.24-7.30 (m, 1H), 7.21 (d, J=2.3 Hz, 1H), 6.55 (t, J=73.7 Hz, 1H), 4.10 (s, 3H). The regioisomeric product, 5-(difluoromethoxy)-3-iodo-2-methyl-2H-indazole, (108 mg, 333 μmol, 18%) was also obtained as a white solid.

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