1,2-dimethyl-1H-imidazole-5-carbaldehyde → {2-Azetidin-1-yl-4-chloro-3-[4-(trifluoromethyl)benzyl]quinolin-6-yl}(1,2-dimethyl-1H-imidazol-5-yl)methanol

Participants

Reaction Conditions

Reaction Steps

2-(Azetidin-1-yl)-6-bromo-4-chloro-3-(4-(trifluoromethyl)benzyl)quinoline (1.00 g, 2.19 mmol, Intermediate 16) was dissolved in THF (20 mL) in a dry round bottom flask under an N2 atmosphere, then cooled to −78° C. in dry ice acetone bath. n-BuLi (1.6 M in hexanes, 1.74 mL, 2.79 mmol) was then added dropwise via syringe over approximately 5 minutes. The contents were stirred at −78° C. for approximately 10 minutes, then a solution of 1,2-dimethyl-1H-imidazole-5-carbaldehyde (0.30 g, 2.4 mmol) in THF (20 mL) was added via cannula and stirred for 10 minutes at −78° C. The dry ice bath was then removed and replaced with an ice water bath and stirred at 0° C. for approximately one hour. The reaction was then quenched with a saturated, aqueous NH4Cl solution, then transferred to a separatory funnel with EtOAc. The organic phase was extracted with a saturated, aqueous NH4Cl solution and deionized water, then separated and dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 0-10% DCM/(10% of a 2 M NH; MeOH in DCM) to provide the title compound. MS (ESI): mass calcd. for C26H24ClF3N4O, 500.2; m/z found, 501.4 [M+H]+. 1H NMR (600 MHz, CDCl3) δ ppm 8.15-8.11 (m, 1H), 7.75 (d, J=8.6 Hz, 1H), 7.57 (dd, J=8.7, 2.0 Hz, 1H), 7.53 (d, J=8.2 Hz, 2H), 7.26-7.21 (m, 2H), 7.59-7.55 (m, 1H), 6.52 (d, 1H), 5.97 (s, 1H), 4.35 (s, 2H), 4.13 (t, J=7.5 Hz, 4H), 3.49 (s, 3H), 2.33 (s, 3H), 2.28-2.20 (m, 2H).

Provenance & Evidence