反应详情

温度

90 °C

Argon is bubbled through a mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine [300 mg, 1.02 mmol, Intermediate (8)], 3-carboxyphenyl boronic acid [339 mg, 2.04 mmol, Intermediate (20)], and Cs2CO3 (1.66 g, 5.1 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL), for a period of 5 minutes. To this mixture is added tetrakis(triphenylphosphine) palladium (0) (59 mg, 0.051 mmol) and the reaction vessel is sealed and heated to 90° C. After stirring for 17 hours the mixture is diluted with water (50 mL) and extracted with EtOAc (50 mL). The aqueous layer is acidified to pH 6 with 10% hydrochloric acid and extracted twice with EtOAc (50 mL). The organic extracts from the acidic solution are combined and dried over magnesium sulfate, filtered and concentrated to provide 3-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzoic acid [350 mg, 90.4%, Example 35(a)] as a solid. LCMS: RT=2.69 minutes, MS: 380 (M+H). 1H NMR [(CD3)2SO]: δ 8.52 (1H, s), 8.28 (3H, m), 8 (2H, m), 7.61 (2H, t, J=0.027 Hz), 7.47 (1H, m), 7.17 (2H, d, J=0.027 Hz), 6.85 (2H, d, J=0.027 Hz), 6.69 (1H, s), 3.89 (3H, s), 3.71 (3H, s), 2.8 (2H, t, J=0.024 Hz).

1. customthe reaction vessel is sealed
2. extractionextracted with EtOAc (50 mL)
3. extractionextracted twice with EtOAc (50 mL)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated