Reaction Steps
To 2-chloro-6-fluoroaniline (0.183 g, 1.259 mmol) and 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added LHMDS (1.0 M solution in THF; 1.259 ml, 1.259 mmol). The reaction was sealed and stirred 1 h at RT, then for 3 h at 70° C. The reaction was subsequently cooled to RT and stirred overnight. 1.5 mL DMSO and 10 drops TFA were added. The mixture was filtered and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-80% ACN/H2O with 0.1% TFA). The product-containing fractions were concentrated in vacuo, and the residue was partitioned between saturated aq. NaHCO3 and DCM. The aq. layer was extracted with DCM (3×), and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was dissolved in DCM/MeOH, adsorbed onto 0.75 g silica gel, and purified by silica gel chromatography using 0-50% 90/10 MeOH/DCM in DCM. The product-containing fractions were concentrated to separately afford 2-(2-((2-chloro-6-fluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.022 g, 0.054 mmol, 21% yield) as a light-yellow solid and 2-(2-((2-chloro-6-fluorophenyl)amino)quinolin-8-yl)-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.0037 g, 9.14 μmol, 4% yield) as a yellow solid. 2-(2-((2-Chloro-6-fluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (7): 1H NMR (400 MHz, DMSO-d6) δ ppm 11.82 (1H, br. s), 9.34 (1H, s), 8.16 (1H, d, J=9.0 Hz), 8.01 (1H, dd, J=7.6, 1.6 Hz), 7.55-7.67 (2H, m), 7.41-7.54 (2H, m), 7.28 (1H, t, J=7.7 Hz), 7.13 (1H, d, J=9.0 Hz), 6.83-6.98 (2H, m), 3.32-3.44 (2H, m), 2.43 (2H, t, J=6.8 Hz). m/z (ESI, +ve) 406.9 (M+H)+. 2-(2-((2-Chloro-6-fluorophenyl)amino)quinolin-8-yl)-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (12): 1H NMR (400 MHz, DMSO-d6) δ ppm 12.09 (1H, br. s), 10.68 (1H, d, J=6.1 Hz), 9.41 (1H, s), 8.11-8.26 (2H, m), 7.43-7.76 (4H, m), 7.34 (1H, t, J=7.7 Hz), 7.18-7.25 (1H, m), 7.14 (1H, d, J=9.0 Hz), 6.86-7.00 (1H, m), 5.91 (1H, d, J=6.8 Hz). m/z (ESI, +ve) 405.2 (M+H)+.
