反应详情

温度

0 °C

To a solution of 4-(tert-butyl)-N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-benzenesulphonamide (Example 2) (1838 mg) in anhydrous THF (18 ml) at 0° C. stirred under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 348 mg) A precipitate began to form which was stirred at 0° C. for 15 min. 2-Chloro-5-nitropyrimidine (Wempen, I.; Blank, H. U.; Fox, J. J. J. Heterocyclic Chem. 1969, 6, 593. Hurst, D. T.; Heterocycles 1984, 22, 79; Heterocycles, 1977, 6, 1999-2004.) (661 mg) in anhydrous DMA (3 ml) was added dropwise and the solution was allowed to warm to room temperature. The reaction was quenched after 130 min by cautiously pouring the mixture onto a vigorously stirred mixture of ethyl acetate (300 ml) and saturated ammonium chloride solution (300 ml). The ethyl acetate layer was separated off, dried (MgSO4) and evaporated to dryness. This afforded a yellow residue (3.44 g) which was purified by column chromatography on silica gel (256 g), eluting with a gradient of ethyl acetate:hexane (4:5 to 5:4).

1. customto form which
2. temperatureto warm to room temperature
3. customThe reaction was quenched after 130 min
4. additionby cautiously pouring the mixture
5. additiononto a vigorously stirred mixture of ethyl acetate (300 ml) and saturated ammonium chloride solution (300 ml)
6. customThe ethyl acetate layer was separated off
7. dry with materialdried (MgSO4)
8. customevaporated to dryness