2,4-Difluoroaniline → 2-(2-((2,4-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Participants

Reaction Conditions

Reaction Steps

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2,4-difluoroaniline (0.178 ml, 1.763 mmol). After 10 min, 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 as a solid and the reaction became dark red. The reaction was heated at 70° C. for 4 h, and then cooled to RT and partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was separated and sequentially washed with saturated aq. NH4Cl and saturated aq. NaCl, and the organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 0-50% 90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford 2-(2-((2,4-difluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.021 g, 0.054 mmol, 21% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.96 (1H, br. s), 9.27 (1H, s), 8.13 (1H, d, J=9.0 Hz), 7.83-8.00 (2H, m), 7.59 (1H, dt, J=7.6, 0.9 Hz), 7.46 (1H, ddd, J=11.2, 8.8, 2.9 Hz), 7.28 (1H, t, J=7.6 Hz), 7.17-7.24 (1H, m), 7.14 (1H, d, J=9.0 Hz), 6.89-6.96 (2H, m), 3.35-3.41 (2H, m), 2.57 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 391.2 (M+H)+.

Provenance & Evidence