反应详情

温度

140 °C

6-(4-Bromo-2-chlorophenyl)-8-ethyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (12, 50 mg, 0.09 mmol), thiophene-2-boronic acid (35 mg, 0.27 mmol), K3PO4 (57 mg, 0.27 mmol) and PdCl2(dppf) (7 mg, 0.01 mmol) were mixed as solids and placed under argon. Argon was bubbled through a mixture of dimethylformamide:water (20:1, 2.0 mL) for 20 min. The solvent was added to the solid and the suspension was heated under microwave irradiation at 140° C. for 30 min. The reaction mixture was evaporated and the crude product was purified by column chromatography, eluting with dichloromethane:methanol (100:3). The product was triturated with refluxing acetonitrile to yield the title compound as a yellow solid (48 mg, 0.09 mmol, 100%). ESMS m/z 557 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.54 (s, 1H), 7.72 (s, 1H), 7.51-7.60 (m, 4H), 7.40 (d, J=8.0 Hz, 1H), 7.30-7.36 (m, 2H), 7.27 (s, 1H), 7.08-7.13 (m, 1H), 6.97 (d, J=8.8 Hz, 2H), 4.50 (q, J=7.0 Hz, 2H), 3.16-3.28 (m, 4H), 2.54-2.69 (m, 4H), 1.39 (t, J=7.0 Hz, 3H).

1. customArgon was bubbled through a mixture of dimethylformamide:water (20:1, 2.0 mL) for 20 min
2. additionThe solvent was added to the solid
3. customThe reaction mixture was evaporated
4. customthe crude product was purified by column chromatography
5. washeluting with dichloromethane:methanol (100:3)
6. customThe product was triturated with refluxing acetonitrile