反应详情

Treat a solution or slurry of the 1-[5-(1-methyl-cyclopropyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-(6-piperazin-1-yl-pyridin-3-yl)-urea (Preparation 5, 1 equiv., 0.1510 g), 2,2-dimethyl pentanoic acid (1.15 equiv., 0.0521 g) and catalytic DMAP (ca. 0.1 equiv., 0.049 g) in dichloromethane (ca. 0.1 M, 5 mL) with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC1.15 equiv., 0.0767 g). Agitate the resulting mixture at ambient temperature for 48 hours then wash with saturated aq. sodium bicarbonate solution. Dry the organic layer over sodium sulfate and concentrate under reduced pressure. Purification A: Purify on silica gel using a gradient 2 M ammonia-methanol in dichloromethane, a gradient of ethyl acetate in dichloromethane or hexanes. Purification B: Purify by reverse phase on an Xterra 30×75 mm 5 micron MS C18 column using a gradient of aqueous 10 mM ammonium bicarbonate in acetonitrile affords the title compound. LCMS(ES+): m/z=544. [M+H].

1. washthen wash with saturated aq. sodium bicarbonate solution
2. dry with materialDry the organic layer over sodium sulfate
3. concentrationconcentrate under reduced pressure
4. customPurification A:
5. customPurify on silica gel using a gradient 2 M ammonia-methanol in dichloromethane
6. customPurification B
7. customPurify by reverse phase on an Xterra 30×75 mm 5 micron MS C18 column