1-BENZYL-5-NITRO-1H-INDAZOLE

Synthesis

100-39-0

5401-94-5

23856-20-4

To a solution of 5-nitroindazole (10.0 g, 61.3 mmol) in acetonitrile (100 mL) was added potassium carbonate (16.9 g, 122.6 mmol) and benzyl bromide (13.6 g, 79.7 mmol). The reaction mixture was heated at 70 °C with stirring overnight. After completion of the reaction, it was cooled to room temperature, the solid was collected by filtration and washed with dichloromethane. The filtrate was concentrated to dryness and the residue was purified by fast column chromatography using a hexane solution of 17-25% ethyl acetate (v/v) as eluent to give 1-benzyl-5-nitro-1H-indazole (7.0 g, 44%) as a yellow solid. Iron powder (4.03 g, 72.1 mmol) was slowly added to a solution of 1-benzyl-5-nitro-1H-indazole (6.9 g, 27.2 mmol) in acetic acid (200 mL). After stirring at room temperature overnight, the reaction mixture became milky and a white precipitate was formed. The precipitate was removed by filtration and the filtrate was concentrated to about 20 mL. The residue was diluted with water (200 mL) and slowly neutralized with sodium hydroxide. Subsequently, the mixture was extracted with ethyl acetate (5 × 100 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to dryness to give 1-benzyl-1H-imidazol-5-ylamine (5.23 g, 82%) as a brown solid. 1H NMR (DMSO-D6): δ 7.72 (s, 1H), 7.35 (d, J = 8.8 Hz, 1H), 7.24-7.14 (m, 5H), 6.74 (m, 2H), 5.49 (s, 2H), 4.80 (br, 2H). ES-LCMS: RT = 0.93 min; [M + H]+ = 224.2.

References