Methanol → HCID 89783180, compound

Participants

Reaction Steps

Similar to the procedure described in Example 103, rac-1,1,1,-trifluoro-2-propanol (Aldrich Chemical Company; 0.18 mL, 2.02 mmol) was added to a suspension of NaH (60% w/w in mineral oil) (81 mg, 2.02 mmol) in DMF (2.0 mL) and the resulting light-green solution was stirred at RT for 10 min. 2-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 75 mg, 0.25 mmol) was then added and the resulting dark red solution was stirred at RT for 5 min, then heated at 70° C. for 2.5 h. The mixture was cooled to RT and partitioned between EtOAc (70 mL) and saturated aq. NH4Cl (50 mL). The organic layer was separated, sequentially washed with water (20 mL) and brine (20 mL), and then dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in DMSO (2.5 mL) and purified by reverse-phase using HPLC (Silicycle column, 20-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min), then dried in a Genevac Series II Evaporator. The residue was chromatagraphically purified then (silica gel; 0-10% MeOH in DCM) affording rac-2-(2-((1,1,1-trifluoropropan-2-yl)oxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (16.0 mg, 0.043 mmol, 16.9% yield) as an amorphous yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.60 (br. s., 1H), 8.39 (d, J=8.8 Hz, 1H), 7.96 (d, J=6.8 Hz, 1H), 7.82 (d, J=7.2 Hz, 1H), 7.52 (t, J=7.7 Hz, 1H), 7.18 (d, J=8.8 Hz, 1H), 7.01 (d, J=2.2 Hz, 1H), 6.95 (br. s., 1H), 6.09 (dt, J=13.5, 6.8 Hz, 1H), 3.40-3.49 (m, 2H), 2.87 (t, J=6.7 Hz, 2H), 1.57 (d, J=6.7 Hz, 3H). 19F NMR (376 MHz, DMSO-d6) δ ppm −77.03 (s, 3F). m/z (ESI, +ve ion) 376.0 (M+H)+.

Provenance & Evidence