(2,4-Dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone → 1-(2,4-Dichloro-3-phenylquinolin-6-yl)-2-methyl-1-(1-methyl-1H-imidazol-5-yl)propan-1-ol

Participants

Reaction Conditions

Reaction Steps

Isopropylmagnesium chloride (2.0 M in THF, 0.056 mL, 0.11 mmol) was added dropwise to a solution of (2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (35 mg, 0.092 mmol, Intermediate 2: step b) in THF (1 mL) at 0° C. The mixture was stirred at 0° C. for 5 minutes, then the ice bath was removed and the mixture was stirred for 25 minutes. The reaction was quenched by the addition of saturated aqueous NH4Cl and was diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The residue was purified by RP-HPLC (10-90% CH3CN—H2O, 0.1% TFA), then was converted to the free base (saturated aqueous NaHCO3/DCM extraction) and re-purified by flash column chromatography (silica gel, 25-70% acetone-EtOAc) to afford the title compound. 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.99 (d, J=8.80 Hz, 1H), 7.62 (d, J=8.80 Hz, 1H), 7.46-7.57 (m, 3H), 7.32-7.39 (m, 2H), 7.28-7.32 (m, 1H), 7.18-7.25 (m, 1H), 3.29 (s, 3H), 2.65-2.76 (m, 1H), 1.24 (d, J=6.60 Hz, 3H), 0.72 (d, J=6.85 Hz, 3H); MS m/e 426.1 (M+H)+.

Provenance & Evidence