4-broMo-5-Methoxy-1H-indazole

Synthesis

29237-10-3

1192004-62-8

General procedure for the synthesis of 4-bromo-5-methoxy-1H-indazole from 3-bromo-4-methoxy-2-methylaniline: 1. 3-Bromo-4-methoxy-2-methylaniline (19.06 g) was dissolved in acetonitrile (250 mL), acetic anhydride (18.9 mL) was added slowly, and the reaction mixture was stirred for 1 hour at room temperature. 2. Potassium acetate (2.60 g) and amyl nitrite (22.3 g) were added to the reaction mixture and heated to reflux for 8 hours. 3. After completion of the reaction, the reaction mixture was concentrated and 6 M hydrochloric acid (200 mL) was added to the residue and heated to reflux overnight. 4. The reaction mixture was neutralized with 8 M sodium hydroxide and subsequently extracted with ethyl acetate. 5. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. 6. The residue was dissolved in tetrahydrofuran, treated with activated charcoal, filtered to remove the activated charcoal and the filtrate was concentrated. 7. The residue was crystallized with diisopropyl ether, the crystals were collected by filtration, washed with diisopropyl ether and dried to obtain the target compound 4-bromo-5-methoxy-1H-indazole (10.42 g, yield 52%) as yellow crystals. Melting point: 178-180°C. Mass spectrum (MS): 229 (MH+).

References