Synthesis
F. Synthesis of 3-methyl-1H-indazole-5-carbonitrile. An aqueous solution (2 mL) of sodium nitrite (3.6 g, 53 mmol) was slowly added dropwise to a solution of glacial acetic acid (150 mL) of 4-amino-3-ethylbenzonitrile (7.0 g, 48 mmol). The reaction mixture was stirred at room temperature for 16 hours and then concentrated under reduced pressure to one-third of the original volume, followed by the addition of water (200 mL). The pH of the aqueous phase was adjusted with saturated sodium bicarbonate solution to 10. The aqueous phase was extracted with ethyl acetate (3 × 200 mL), the organic extracts were combined and dried with anhydrous magnesium sulfate. After concentration of the organic phase under reduced pressure, the crude product was purified by rapid chromatography on silica gel (eluent: 0-45% hexane solution of ethyl acetate) to afford 3-methyl-1H-indazole-5-carbonitrile as an orange solid (3.3 g, 21 mmol, 30% yield). Mass spectrum (ESI) m/z 158.2 [M + H]+.
