反应详情

温度

80 °C

A sealable vial, was charged with 4-carbamoylphenylboronic acid (0.0312 g, 0.189 mmol), N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 0.100 g, 0.0947 mmol), Cs2CO3 (0.0309 g, 0.0947 mmol), toluene (2 mL) and EtOH (1 mL). Under nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added and the reaction heated to 80° C. for 18 hours. The mixture was then cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (30 mL) and MeOH (2 mL). The organics were dried over sodium sulfate, filtered and concentrated to get crude product. The crude product was purified by reverse phase C-18 column chromatography to get product (6.9 mg, 13%) as a white solid. LRMS (esi+) 585 m/z (M+1) detected. 1H NMR (d6-DMSO, 400 MHz) δ 8.48 (d, J=6 Hz, 1H), 7.96 (m, 5H), 7.87 (m, 1H), 7.57 (m, 2H), 7.37 (m, 2H), 7.07 (t, J=9.0 Hz, 2H), 6.65 (d, J=6 Hz, 1H), 1.64 (s, 4H).

1. additionUnder nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added
2. temperatureThe mixture was then cooled to room temperature
3. extractionextracted with ethyl acetate (30 mL) and MeOH (2 mL)
4. dry with materialThe organics were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto get crude product
8. customThe crude product was purified by reverse phase C-18 column chromatography