2075-46-9

33064-36-7

This Example illustrates the preparation of compound 108, 3-pyridine carboxylic acid, 5-[(4-amino-1H-pyrazol-1-yl)carbonyl]-2-methoxy-4-(2-methylpropyl)-6-(trifluoromethyl)-, methyl ester. A tetrahydrofuran (THF, 100 mL) solution of 4-nitropyrazole (22.62 g, 200 mmol) was cooled to 0 °C, followed by slow dropwise addition of a THF solution of sodium bis(trimethylmethylsilyl)amide (204.3 mmol) at 0 °C. Subsequently, a THF (100 mL) solution of compound 84 (70.75 g, 200 mmol) was added slowly dropwise at 0 °C. After the dropwise addition was completed, the reaction mixture was stirred at 25 °C for 30 min. After completion of the reaction, the mixture was poured into 5% hydrochloric acid solution and extracted with dichloromethane. The organic layer was dried with anhydrous magnesium sulfate (MgSO?) and the solvent was subsequently removed by rotary evaporator. The residue was purified by silica gel column chromatography (eluent: 5% ethyl acetate/hexane) to afford pyrazolamide (compound 101) 70.14 g in 82% yield.