Reaction Steps
(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (100 mg, 0.164 mmol, Intermediate 65), N,O-dimethylhydroxylamine hydrochloride (327 mg, 2.82 mmol), and dimethylformamide (2 mL) were combined in a reaction tube, which was then sealed and heated to 100° C. for 48 hours. The contents were then cooled, transferred to a separatory funnel, diluted with EtOAc, extracted with a saturated, aqueous NH4Cl solution, then four times with deionized water. The organic phase was separated and 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 C34H33F3N8O3, 658.3. m/z found, 659.3 [M+H]+. 1H NMR (600 MHz, CD3OD) δ 8.75 (d, J=2.1 Hz, 1H), 8.34 (d, J=2.0 Hz, 1H), 8.13 (dd, J=2.5, 0.5 Hz, 1H), 8.01 (dd, J=8.6, 2.7 Hz, 2H), 7.84 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.75 (dd, J=8.9, 2.2 Hz, 1H), 7.69-7.65 (m, 1H), 7.60-7.55 (m, 2H), 7.21 (d, J=8.7 Hz, 2H), 6.48 (dd, J=2.4, 1.9 Hz, 1H), 6.38 (s, 1H), 4.43 (s, 2H), 3.51 (s, 3H), 3.46 (s, 3H), 3.13 (s, 3H), 3.30 (s, 3H), 2.89 (s, 3H).
