反应详情

温度

60 °C

A mixture of methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate (isomer 1, early eluting) (100 mg, 0.2 mmol) and lithium hydroxide monohydrate (26 mg, 0.6 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 60° C. for 3 hours. After being cooled to 0° C., the mixture was adjusted to pH 7 with aqueous sodium bicarbonate solution. Then the mixture was extracted with ethyl acetate and washed by brine. The organic layer was concentrated and the residue was purified by reverse phase chromatography to afford 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoic acid (Example 19.7). MS ESI calc'd. for C24H21F3N5O3 [M+H]+ 484. found 484. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 9.66 (s, 1H), 8.99 (s, 1H), 8.93 (s, 1H), 8.69-8.71 (m, 2H), 8.42-8.44 (m, 3H), 8.24 (s, 1H), 8.10-8.11 (m, 2H), 6.67 (s, 1H), 3.16 (s, 3H), 2.64 (s, 3H).

1. temperatureAfter being cooled to 0° C.
2. extractionThen the mixture was extracted with ethyl acetate
3. washwashed by brine
4. concentrationThe organic layer was concentrated
5. customthe residue was purified by reverse phase chromatography