Reaction Steps
(2,4-Dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl) [6-(trifluoromethyl) pyridin-3-yl]methanol (200 mg, 0.378 mmol, Example 66), 2,2,2-trifluoroethanol (14.0 μL, 0.19 mmol), toluene (2 mL), and sodium hydride (60% dispersion in mineral oil, 19 mg, 0.47 mmol) were combined in a round bottom flask under an N2 atmosphere. The reaction solution was heated to reflux and refluxed overnight. Analysis showed the reaction had only progressed a moderate amount, so additional reagents were added, 2,2,2-trifluoroethanol (14.0 μL, 0.19 mmol) and sodium hydride (60% dispersion in mineral oil, 6 mg, 0.19 mmol) and contents were heated at reflux for an additional 48 hours. The contents were cooled to room temperature then transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl then saturated, aqueous NaHCO3 solutions. The organic phase was separated then dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with 0.05% trifluoroacetic acid in water as eluent. The fractions from the purification containing the desired product were transferred to a separatory funnel with EtOAc and extracted with a saturated, aqueous NaHCO3 solution. The aqueous layer was separated, extracted with EtOAc, then the combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound. MS (ESI): mass calcd. for C28H19ClF6N4O2, 592.1; m/z found, 593.2 [M+H]+; 1H NMR (600 MHz, CD3OD) δ ppm 8.80 (d, J=2.1 Hz, 1H), 8.28 (d, J=1.9 Hz, 1H), 8.17 (s, 1H), 8.05 (dd, J=8.2, 2.0 Hz, 1H), 7.97 (d, J=8.7 Hz, 1H), 7.86 (dd, J=8.3, 0.4 Hz, 1H), 7.75 (dd, J=8.8, 2.2 Hz, 1H), 7.51-7.42 (m, 3H), 7.37-7.34 (m, 2H), 6.60 (s, 1H), 5.00 (q, J=8.6 Hz, 2H), 3.56 (s, 3H).
