反应详情

温度

85 °C

To a sealable vial containing 1-(5-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (0.05 g, 0.101 mmol) was added phenylboronic acid (0.018 g, 0.151 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.016 g, 0.020 mmol), K2CO3 (0.06 g, 0.434 mmol), 1,4-dioxane (2 mL), and water (0.5 mL). The vessel was flushed with N2, then the vial was sealed and heated to 85° C. After 2 h the mixture was cooled to rt, and concentrated under reduced pressure. The residue was diluted with water (30 mL) and extracted with dichloromethane (3×30 mL). The organic solution was dried with Na2SO4, the drying agent was removed by filtration, and the organic solution was concentrated under reduced pressure. The residue was purified by prep HPLC. Some impurities were still present by LC/MS, so the mixture was further purified by flash chromatography using a 0-5% MeOH in dichloromethane gradient. The expected product, 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)ethane-1,2-dione (0.024 g, 0.049 mmol, 48.3% yield), was isolated as an off-white solid. LC/MS: m/z 493.25 (M+H)+, 2.12 min (method 1). 1H NMR (500 MHz, chloroform-d) δ ppm 11.01 (br. s., 1H) 9.14 (s, 1H) 8.19-8.27 (m, 1H) 7.67-7.72 (m, 1H) 7.01-7.50 (m, 8H) 4.74-5.00 (m, 2H) 3.67-3.87 (m, 5H) 2.79-2.98 (m, 2H) 2.55-2.61 (m, 3H).

1. customThe vessel was flushed with N2
2. customthe vial was sealed
3. temperatureAfter 2 h the mixture was cooled to rt
4. concentrationconcentrated under reduced pressure
5. additionThe residue was diluted with water (30 mL)
6. extractionextracted with dichloromethane (3×30 mL)
7. dry with materialThe organic solution was dried with Na2SO4
8. customthe drying agent was removed by filtration
9. concentrationthe organic solution was concentrated under reduced pressure
10. customThe residue was purified by prep HPLC
11. customwas further purified by flash chromatography