2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one → 2-(2-benzylquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Participants

Reaction Conditions

Reaction Steps

Argon was bubbled through a slurry of bis(4-(di-tert-butylphosphino)-N,N-dimethylbenzenamine)palladium dichloride (Aldrich; 10.23 mg, 0.014 mmol), 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1, 0.043 g, 0.144 mmol), and benzylzinc bromide (0.5 M solution in THF; Aldrich; 1.155 ml, 0.578 mmol) in 1.5 mL THF for 2 min. The reaction mixture was sealed and heated to 70° C. After 1 h, the reaction was cooled to RT. The mixture was concentrated, dissolved in DMSO+1-2 drops TFA, filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 15-100% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo and the residue was treated with saturated aq. NaHCO3 and DCM. The aq. layer was extracted 3×DCM and combined organics dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-benzylquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.026 g, 0.074 mmol, 50.9% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 12.17 (1H, br. s), 8.35 (1H, d, J=8.6 Hz), 8.14 (1H, dd, J=7.4, 1.4 Hz), 7.76 (1H, dd, J=8.0, 1.4 Hz), 7.50-7.60 (2H, m), 7.33-7.43 (4H, m), 7.24-7.30 (1H, m), 7.11 (1H, d, J=2.3 Hz), 6.94-7.00 (1H, m), 4.45 (2H, s), 3.38-3.46 (2H, m), 2.80 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 353.9 (M+H)+.

Provenance & Evidence