Reaction SMILES: [N:1]1([C:6]2[CH:42]=[CH:41][C:9]([CH2:10][C:11]3[C:12](Cl)=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:34]3[N:38]([CH3:39])[CH:37]=[N:36][CH:35]=3)([C:24]3[CH:25]=[N:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[OH:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.Cl.[CH3:44][NH:45][O:46][CH3:47].CN(C)C=O>C(OCC)(=O)C>[N:1]1([C:6]2[CH:42]=[CH:41][C:9]([CH2:10][C:11]3[C:12]([N:45]([O:46][CH3:47])[CH3:44])=[N:13][C:14]4[C:19]([C:20]=3[Cl:21])=[CH:18][C:17]([C:22]([C:34]3[N:38]([CH3:39])[CH:37]=[N:36][CH:35]=3)([C:24]3[CH:25]=[N:26][C:27]([C:30]([F:32])([F:31])[F:33])=[CH:28][CH:29]=3)[OH:23])=[CH:16][CH:15]=4)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: CNOC
Reactant: Cn1cncc1C(O)(c1ccc(C(F)(F)F)nc1)c1ccc2nc(Cl)c(Cc3ccc(-n4cccn4)cc3)c(Cl)c2c1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CON(C)c1nc2ccc(C(O)(c3ccc(C(F)(F)F)nc3)c3cncn3C)cc2c(Cl)c1Cc1ccc(-n2cccn2)cc1
Temperature: 100 °C

Procedure:
To a 5 mL sealed tube was added (3-(4-(1H-pyrazol-1-yl)benzyl)-2,4-dichloroquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (250 mg, 0.41 mmol, 1 equivalent, Example 23, free base), N,O-dimethylhydroxylamine hydrochloride (327 mg, 3.28 mmol, 10 equivalents) and dimethylformamide (2 mL). The reaction vessel was sealed and heated in a 100° C. oil bath. After overnight reaction, the vessel was cooled and contents transferred to a separatory funnel with ethyl acetate dilution. The organic phase was extracted with saturated, aqueous ammonium chloride solution and deionized water. The organic phase was separated, dried over magnesium sulfate, filtered and evaporated to dryness under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with 0.05% trifluoroacetic acid in water as eluent to provide racemic (3-(4-(1H-pyrazol-1-yl)benzyl)-4-chloro-2-(methoxy(methyl)amino)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol; MS (ESI): mass calcd. for C32H27ClF3N7O2, 633.19; m/z found, 634.3 [M+H]+. 1H NMR (600 MHz, MeOH-d4) δ ppm 8.79 (d, J=2.1 Hz, 1H), 8.22 (d, J=2.0 Hz, 1H), 8.13-8.10 (m, 1H), 8.02 (dd, J=8.3, 2.1 Hz, 1H), 7.99 (d, J=8.8 Hz, 1H), 7.82 (d, J=8.3 Hz, 1H), 7.79 (s, 1H), 7.72 (dd, J=8.8, 2.1 Hz, 1H), 7.67 (d, J=1.7 Hz, 1H), 7.59-7.56 (m, 2H), 7.24 (d, J=8.7 Hz, 2H), 6.50-6.45 (m, 1H), 6.39 (s, 1H), 4.42 (s, 2H), 3.49 (s, 3H), 3.45 (s, 3H), 3.16 (s, 3H). Racemic (3-(4-(1H-pyrazol-1-yl)benzyl)-4-chloro-2-(methoxy(methyl)amino)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol was purified on a chiralcel OD column (20 um, Diacel) with ethanol/heptanes to provide two enantiomers. The first eluting enantiomer was Example 67B: MS (ESI): mass calcd. for C32H27ClF3N7O2, 633.19; m/z found, 634.3 [M+H]+. 1H NMR (600 MHz, MeOH-d4) δ ppm 8.80 (d, J=2.0 Hz, 1H), 8.23 (d, J=1.9 Hz, 1H), 8.10 (dd, J=2.5, 0.4 Hz, 1H), 8.01 (dd, J=8.2, 2.0 Hz, 1H), 7.98 (d, J=8.9 Hz, 1H), 7.81 (d, J=8.2 Hz, 1H), 7.73 (s, 1H), 7.71 (dd, J=8.8, 2.1 Hz, 1H), 7.66 (d, J=1.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.25-7.20 (m, 2H), 6.46 (dd, J=2.4, 1.9 Hz, 1H), 6.37 (s, 1H), 4.39 (s, 2H), 3.47 (s, 3H), 3.44 (s, 3H), 3.16 (s, 3H) and the second eluting enantiomer was Example 67C: MS (ESI): mass calcd. for C32H27ClF3N7O2, 633.19; m/z found, 634.3 [M+H]+. 1H NMR (600 MHz, MeOH-d4) δ ppm 8.80 (d, J=2.0 Hz, 1H), 8.23 (d, J=2.0 Hz, 1H), 8.12-8.09 (m, 1H), 8.01 (dd, J=8.2, 2.1 Hz, 1H), 7.98 (d, J=8.8 Hz, 1H), 7.81 (d, J=8.2 Hz, 1H), 7.73 (s, 1H), 7.71 (dd, J=8.8, 2.1 Hz, 1H), 7.67 (d, J=1.5 Hz, 1H), 7.59-7.54 (m, 2H), 7.25-7.20 (m, 2H), 6.47 (dd, J=2.4, 1.9 Hz, 1H), 6.37 (s, 1H), 4.40 (s, 2H), 3.47 (s, 3H), 3.44 (s, 3H), 3.16 (s, 3H).