反应详情

To a 150 mL flask, methanesulfonyl chloride (1.1 g, 9.8 mmol), acetonitrile (20 mL) was added. Then the mixture of 3-bromo-1-(3,5-dichloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid (3.0 g, 8.9 mmol, the product of step (3), example 4) and triethylamine (0.89 g, 8.9 mmol) in acetonitrile (30 mL) were added dropwise in 10 minutes at room temperature. The mixture was stirred for 1 hour. 2-Amino-3,5-dichlorobenzoic acid (1.6 g, 17 mmol) was added, and the reaction mixture turned into reddish brown. After being stirred for 30 minutes, the solution of triethylamine (1.8 g, 17 mmol) in acetonitrile (10 mL) was added dropwise and yellow solid precipitated. The mixture was stirred for 1 hour, another solution of methanesulfonyl chloride (1.1 g, 9.8 mmol) in acetonitrile (10 mL) was added. The reaction mixture turned into yellow and solid was precipitated. After being stirred for 1 hour, another solution of triethylamine (0.89 g, 8.9 mmol) in acetonitrile (4 mL) was added. Then the reaction mixture was stirred for overnight at room temperature. The reaction mixture was poured into water (100 mL), extracted with ethyl acetate (2×100 mL), washed with saturated sodium carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (Fluent: ethyl acetate/petroleum ether=1/2) to give the product (2.0 g) as a yellow solid in 45% yield.

1. stirringAfter being stirred for 30 minutes
2. customyellow solid precipitated
3. stirringThe mixture was stirred for 1 hour
4. customwas precipitated
5. stirringAfter being stirred for 1 hour
6. stirringThen the reaction mixture was stirred for overnight at room temperature
7. extractionextracted with ethyl acetate (2×100 mL)
8. washwashed with saturated sodium carbonate solution and saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated
11. customThe residue was purified by silica gel column chromatography (Fluent: ethyl acetate/petroleum ether=1/2)