反应详情

温度

120 °C

N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide (46 mg, 0.15 mmol), 4-chlorothieno[3,2-d]pyrimidine (17 mg, 0.10 mmol), cesium carbonate (49 mg, 0.15 mmol), and copper(I) chloride (10 mg, 0.10 mmol) were placed in a test tube. The tube was sealed, flushed with nitrogen, charged with 1-methyl-2-pyrrolidinone (0.3 mL) followed by 2,2,6,6-tetramethyl-3,5-heptanedione (4.0 μL, 0.02 mmol). The reaction was stirred at 120° C. for 2 h. The reaction mixture was purified by preparative HPLC. The appropriate fraction was concentrated to remove methanol and the resulting aqueous solution was made basic with saturated NaHCO3 solution (5 mL). The aqueous solution was extracted with EtOAc (3×10 mL) and the combined organic extracts were dried over anhydrous Na2SO4 and concentrated in vacuo to give the desired product as a colorless oil. Lyophilization with methanol/water gave the title compound (23 mg, 52%) as a white solid. 1H NMR (CD3OD) δ 8.54 (s, 1H), 8.21 (d, 1H, J=5.5 Hz), 7.69 (dd, 1H, J=12.4, 2.0 Hz), 7.49 (m, 3H), 7.27 (m, 2H), 6.96 (t, 2H, J=8.9 Hz), 3.47 (s, 2H); MS(ESI+) m/z 441.1 (M+H)+.

1. customThe tube was sealed
2. customflushed with nitrogen
3. additioncharged with 1-methyl-2-pyrrolidinone (0.3 mL)
4. customThe reaction mixture was purified by preparative HPLC
5. concentrationThe appropriate fraction was concentrated
6. customto remove methanol
7. extractionThe aqueous solution was extracted with EtOAc (3×10 mL)
8. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
9. concentrationconcentrated in vacuo