Reaction Steps
2-(2-Chloroquinolin-8-yl)-6-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 31; 0.050 g, 0.160 mmol) and aniline (0.073 ml, 0.802 mmol) were treated with LHMDS (1.0 M solution in THF; 1.203 ml, 1.203 mmol). The dark red reaction was stirred for 3 h, at which point it was concentrated then treated with DMSO and TFA (0.185 ml, 2.406 mmol). This material was purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-80% ACN/H2O with 0.1% TFA); product-containing fractions were treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give rac-6-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.018 g, 0.050 mmol, 31% yield, Example 237) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.15 (1H, br. s), 9.52 (1H, s), 8.11 (1H, d, J=9.0 Hz), 7.93 (1H, dt, J=7.4, 0.9 Hz), 7.65 (2H, d, J=7.6 Hz), 7.58 (1H, dt, J=7.7, 1.0 Hz), 7.40 (2H, t, J=7.9 Hz), 7.28 (1H, t, J=7.7 Hz), 7.02-7.15 (2H, m), 6.82-6.97 (2H, m), 3.75 (1H, dt, J=11.3, 5.8 Hz), 2.65 (1H, dd, J=15.6, 5.3 Hz), 2.36-2.47 (1H, m), 1.23 (3H, d, J=6.3 Hz). m/z (ESI, +ve) 369.2 (M+H)+. A portion of this material was resolved by chiral SFC (Chiralcel IC-H (150×21 mm, 5 μm); additive in supercritical fluid CO2 was 40% EtOH with 40 mM NH3; 70 mL/min; column temperature 40° C.; outlet pressure 100 bar) to give separated enantiomers 6-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 33, first eluting enantiomer) and 6-methyl-2-(2-(phenylamino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 34, second eluting enantiomer).
