反应详情

温度

110 °C

To a solution of 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid [100 mg, 0.218 mmol, Example 49(b)] in dimethylformamide (2 mL) is added 1-chloroethyl ethyl carbonate (0.053 mL, 0.392 mmol) and Cs2CO3 (142 mg, 0.436 mmol). The mixture is heated under microwave at 110° C. for 10 minutes, quenched with water, and extracted with ethyl acetate. Combined organic layers are washed with brine, dried over sodium sulfate and concentrated. The residue is subjected to silica gel chromatography eluting with 0 to 40% EtOAc in heptane to obtain 2-(3-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester as an oil 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)-2-methyl-propionic acid 1-ethoxycarbonyloxy-ethyl ester hydrochloride [80 mg, 64%, Example 50] as a solid. LC/MS: RT=2.94 minutes, MS: 576 (M+H). 1H NMR [300 MHz, (CD3)2SO]: □7.36-7.8 (7H, m), 6.64 (1H, q), 6.6 (1H, s), 4.05 (2H, q), 3.96 (3H, s), 3.68 (2H, m), 3 (2H, m), 1.57 (6H, s), 1.38 (3H, d), 1.15 (3H, t). IC50=4 nM

1. customquenched with water
2. extractionextracted with ethyl acetate
3. washCombined organic layers are washed with brine
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated
6. washeluting with 0 to 40% EtOAc in heptane