反应详情

温度

90 °C

Argon is bubbled through a mixture of {4-chloro-6-[2-(2,4-dichloro-phenyl)-ethylamino]-pyrimidin-2-yl}-methanol (67 mg, 0.2 mmol), 3-(1-Carboxy-1-methyl-ethyl)-phenyl boronic acid [92 mg, 0.44 mmol, see Example 49(b) step 2], Cs2CO3 (197 mg, 0.6 mmol), and tetrakis(triphenylphosphine)palladium (0) (16.3 mg, 0.014 mmol) in ethylene glycol dimethyl ether (1.6 mL) and water (0.4 mL), for a period of 10 minutes. The reaction vessel is sealed and heated to 90° C. After stirring for 16 hours the mixture is diluted with water (25 mL, brought to pH 4 with HCl and extracted thrice with EtOAc (25 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and concentrated to afford 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-hydroxymethyl-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [16.5 mg, 18%, Example 86] as a solid. LCMS RT=2.47 minutes, MS: 460 (M+H). IC50=71 nM

1. customThe reaction vessel is sealed
2. extractionextracted thrice with EtOAc (25 mL)
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated