反应详情

To a mixture of 5-bromo-1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indole (150 mg, 0.426 mmol), bis(pinacolato)diboron (114 mg, 0.447 mmol), and potassium acetate (125 mg, 1.278 mmol) was added 1,4-dioxane (6 mL), and the mixture was degassed with N2 for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (17.39 mg, 0.021 mmol) was added, and the reaction mixture was stirred for 3 hours at 100 C into a sealed vessel. The reaction was cooled down to room temperature. 5-bromothieno[2,3-d]pyrimidin-4-amine (103 mg, 0.447 mmol) and sat. aq. NaHCO3 (2 mL) were added, and N2 gas was bubbled through the mixture for 10 minutes. PdCl2(dppf)-CH2Cl2 adduct (17.39 mg, 0.021 mmol) was added, the vessel was sealed, and the reaction mixture was stirred overnight at 100 C. The mixture was poured onto water and a precipitate was formed. The mixture was filtered, and the solid was taken up into a mixture of 20% CH3OH/CH2Cl2 mixture, and the resulting mixture was filtered, injected into a 90 g silica gel column, and purified via flash chromatography (gradient: 100% Hexanes to 100% EtOAc). The fractions containing the product were combined and concentrated to afford a solid. Trituration with Et2O afforded 5-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}thieno[2,3-d]pyrimidin-4-amine (120 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 3.27 (t, 2H), 3.96 (s, 2H), 4.31 (t, J=8.46 Hz, 2H), 7.13-7.32 (m, 4H), 7.37 (s, 1H), 7.43 (s, 1H), 8.11 (d, J=8.08 Hz, 1H), 8.34 (s, 1H).

1. customthe mixture was degassed with N2 for 10 minutes
2. customN2 gas was bubbled through the mixture for 10 minutes
3. customthe vessel was sealed
4. stirringthe reaction mixture was stirred overnight at 100 C
5. additionThe mixture was poured onto water
6. customa precipitate was formed
7. filtrationThe mixture was filtered
8. additionthe solid was taken up into a mixture of 20% CH3OH/CH2Cl2 mixture
9. filtrationthe resulting mixture was filtered
10. custompurified via flash chromatography (gradient: 100% Hexanes to 100% EtOAc)
11. additionThe fractions containing the product
12. concentrationconcentrated
13. customto afford a solid