反应详情

温度

130 °C

A solution of (6-chloro-2-methoxy-pyrimidin-4-yl)-[2-(2,4-dichloro-phenyl)-ethyl]-amine [170 mg, 0.51 mmol, Intermediate (44)] and 3-(1-carboxy-ethyl)-phenyl boronic acid [119 mg, 0.61 mmol, Intermediate (70)] in acetonitrile (2.5 mL) and aqueous Na2CO3 solution (0.4 M, 2.5 mL) is degassed with nitrogen for 5 minutes before addition of tetrakis(triphenylphosphine)palladium (0) (29.5 mg, 5 mol %). The reaction vessel is sealed and heated under microwave to 130° C. for 30 minutes. To the reaction mixture is added 2 mL of water, the pH is adjusted to about 7 using 2 N aqueous hydrochloric acid and this mixture is extracted three times with EtOAc (30 mL). The combined extracts are washed with brine, dried over sodium sulfate and concentrated. The resulting oil is subjected to silica gel chromatography eluting with 0 to 7% MeOH in DCM to give 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid as a solid, which is treated with 1M hydrogen chloride in ether affording 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-propionic acid hydrochloride [122 mg, 50%, Example 49(a)] as a solid. LC/MS: RT=2.47 minutes, MS: 446 (M+H). 1H NMR [300 MHz, (CD3)2SO]: □12.4 (1H, br s), 7.36-7.8 (7H, m), 6.6 (1H, s), 4 (3H, s), 3.78 (1H, q), 3.68 (2H, m), 3.02 (2H, m), 1.42 (3H, d). IC50=1 nM

1. customThe reaction vessel is sealed
2. extractionthis mixture is extracted three times with EtOAc (30 mL)
3. washThe combined extracts are washed with brine
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. washeluting with 0 to 7% MeOH in DCM