(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone → 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)ethanol

Participants

Reaction Conditions

Reaction Steps

To a flask containing (4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1,2-dimethyl-1H-imidazol-5-yl)methanone (408 mg, 0.86 mmol, Intermediate 8: step b) was added THF (20 mL) and the solution was cooled to −78° C. MeLi (1.6 M in Et2O, 0.6 mL, 0.96 mmol) was then introduced. After 25 minutes, the reaction mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (4×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (5% MeOH-DCM increasing to 10% MeOH) provided the title compound as a white amorphous solid. 1H NMR (500 MHz, CDCl3) δ 8.26 (d, J=1.7 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.2 Hz, 3H), 7.40 (d, J=8.1 Hz, 2H), 7.04 (d, J=10.7 Hz, 1H), 4.35 (s, 2H), 4.07 (s, 3H), 3.14 (s, 3H), 2.29 (s, 3H), 1.95 (s, 3H); MS (ESI): mass calcd. for C25H23ClF3N3O2, 489.1, m/z found 490.1 [M+H]+. 1-(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)-1-(1,2-dimethyl-1H-imidazol-5-yl)ethanol was purified by chiral chromatography (Chiracel OD (20 μM) diacel, 50×41 cm, heptane:ethanol with 2% isopropylamine (90:10)), to give 2 enantiomers. The first eluting enantiomer was Example 12b and the second eluting enantiomer was Example 12c.

Provenance & Evidence