Potassium Carbonate → 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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence