Trifluoroacetic acid → 2-(2-(2-chloro-6-fluorophenoxy)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-chloro-6-fluorophenol (0.258 g, 1.763 mmol). After 10 min, a clear/colorless solution resulted. 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 and the reaction became dark red. The reaction was heated at 70° C. for 1 h, then at 90° C. for 2 h, then at 110° C. for 14 h. The reaction was cooled to 0° C. and quenched with TFA (0.136 ml, 1.763 mmol), diluted with 1 mL DMSO, 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 then treated with saturated aq. NaHCO3 and DCM. The organic layer was separated and the aq. layer was extracted 3×DCM. The combined organic extracts were then dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-(2-chloro-6-fluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.030 g, 0.074 mmol, 29% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.91 (1H, br. s), 8.57 (1H, d, J=8.8 Hz), 8.05-8.15 (1H, m), 7.84 (1H, dt, J=7.7, 0.8 Hz), 7.38-7.69 (5H, m), 6.87-6.91 (1H, m), 6.85 (1H, d, J=2.3 Hz), 3.32-3.38 (2H, m), 2.54-2.50 (2H, m). m/z (ESI, +ve) 408.2 (M+H)+.

Provenance & Evidence