78% |
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃; for 5h; |
5.38g (20.0 mmol) of <strong>[141474-37-5]2,4-dibromo-6-fluoro-phenylamine</strong>, 5.36 g (44.0 mmol) of phenylboronic acid, 1.15 g (1.0 mmol) of Pd(PPh3)4, and 8.29 g (60.0 mmol) of K2CO3 were dissolved in 80 mL of a mixed solution THF/H2O (2:1) to obtain a solution, which was then stirred at about 70C for about 5 hours. The reaction solution was cooled to room temperature, followed by three times of extraction with 60 mL of water and 60 mL of diethylether. The organic phase was collected, and was dried using magnesium sulfate to evaporate the solvent. The residue was separated and purified using silica gel column chromatography to obtain 4.11 g of Intermediate I-29 (Yield: 78 %) This compound was identified using LC-MS and NMR. C18H14FN : M+ 263.1 1H NMR (CD2Cl2, 400MHz) delta (ppm) 7.62-7.57 (t, 1H), 7.56-7.54 (m, 1H), 7.51-7.47 (m, 4H), 7.44-7.37 (m, 3H), 7.31-7.30 (m, 1H), 7.29-7.26 (m, 1H), 7.23-7.22 (m, 1H), 3.94 (s, 2H) |
75% |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 5h; |
5.37 g (20.0 mmol) of <strong>[141474-37-5]2,4-dibromo-6-fluoro-phenylamine</strong>, 4.88 g (40.0 mmol) of a phenylboronic acid, 1.15 g (1.0 mmol) of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) and 8.29 g (60.0 mmol) of K2CO3 were dissolved in 60 ml of a mixed solution of THF/H2O (volumetric ratio of 2/1), and then stirred at a temperature of 70 C. for 5 hours. The reaction solution was cooled to room temperature and 40 ml of water was added, followed by extraction three times with 50 ml of ethylether. A collected organic layer was dried with a magnesium sulfate and the residual obtained by evaporating a solvent was separation-purified by silicagel column chromatography to obtain 3.95 g (Yield 75%) of Intermediate I-11. The formed compound was confirmed by MS/FAB. C18H14FN: calc. 263.11, found 263.25. |
70% |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene;Reflux; Inert atmosphere; |
Are added respectively in the container for 2nd 2.69g (0.01mole) intermediate G5-1, phenyltheophylline boric acid 2.44g (0.02mole), potassium carbonate 4.15g (0.03mole), toluene 50 ml, ethanol 30 ml and water 30 ml, under a nitrogen atmosphere, by adding four (triphenylphosphine) palladium 0.23g (0.0002mole), heating to reflux for reaction, monitoring board to the reaction is complete, turn off the heating, turns on lathe does, by adding 100 ml of methylene chloride, the silica gel and completely dissolved, the filtrate by adding 100 ml water, washing with water, the organic phase is separated, fasten it dry and heat two times with ethanol, filtered, the solid intermediate kind of white G5-2, the yield is 70%. |
20 g |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 120℃; for 7h; |
Preparationofcompound 4-1After adding <strong>[141474-37-5]2,4-dibromo-6-fluoroaniline</strong> (25.0 g, 92.9 mmol), phenylboronic acid (34.0 g, 278.0 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (10.0 g, 9.29 mmol) and K2C03 (64.0 g, 464.0 mmol) to a mixed solution of toluene (300.0 ml), ethanol (EtOH) (100.0 ml) and H20 (100.0 ml) and dissolving the reaction mixture, and the mixture was stuffed for 7 hours at 120C. After completing the reaction by slowly adding H20, the organic layer was extracted with EA, was dried with Na2SO4, and was separated through column chromatography to obtain compound 4-1(20.0 g). |