Synthesis
To a solution of 3,4,5-tribromopyrazole (60 g) in acetic acid (900 mL) was slowly added 90% fuming nitric acid (21 mL) at 10 °C. Subsequently, acetic anhydride (300 mL) was added dropwise over 20 minutes. The reaction system was gradually warmed to room temperature and stirred continuously for 3 hours. Upon completion of the reaction, the mixture was poured onto ice and a white solid precipitated. The precipitate was collected by filtration and washed with water (200 mL). The resulting solid was dissolved in toluene (750 mL), the organic phase was washed sequentially with water (200 mL) and saturated saline (100 mL), dried over anhydrous sodium sulfate and filtered. To this toluene solution was added 3,5-dimethyl-1H-pyrazole (20 g) and heated to reflux for 20 min. The reaction solution was cooled and concentrated under reduced pressure. The crude product was ground with heptane, the precipitate was collected by filtration and dried under vacuum to give a crude product containing mainly the target product (71.7 g, 67.6% yield), which could be used directly in the next reaction.
The reduction reaction was carried out by refluxing 3,4-dibromo-5-nitro-1H-pyrazole (69 g) prepared above with stannous chloride dihydrate (135 g) in a mixed solvent of ethyl acetate (600 mL) and ethanol (300 mL) at 110 °C for 45 min. After the reaction was completed, the yellow homogeneous solution was cooled to room temperature and slowly poured into a vigorously stirred mixture of aqueous sodium bicarbonate (33 g) (200 mL) and ethyl acetate (800 mL). Diatomaceous earth (30 g) was added to aid filtration, filtered, and the filter cake was washed with ethyl acetate (600 mL). The organic phases were combined, washed with saturated saline (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give an orange oily crude product. Purification by fast column chromatography (Biotage, Quad 25; eluent: dichloromethane solution of 6% ethanol) gave the title compound as a light beige solid (13.2 g, 32% yield).
1H NMR (400 MHz, DMSO-d6) δ: 5.20 (m, 3H), 11.60 (br s, 1H).
