Toluene → [4-Chloro-2-(2-methoxyethoxy)-3-phenylquinolin-6-yl](4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

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Reaction Steps

(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (100 mg, 0.202 mmol, Example 65), 2-methoxyethanol (16.0 μL, 0.202 mmol), toluene (2 mL), and sodium hydride (60% dispersion in mineral oil, 20.2 mg, 0.505 mmol) were combined in a round bottom flask under an N2 atmosphere. The contents were heated to reflux and refluxed overnight. The reaction solution turned from a heterogeneous white mixture to slightly yellowish with a moderate amount of precipitate. The contents were cooled to room temperature then transferred to a separatory funnel with EtOAc dilution, and extracted with saturated, aqueous NH4Cl and saturated, aqueous NaHCO3 solutions. The organic phase was separated then 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 NH3 MeOH in DCM)) then further purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C29H25Cl2N3O3, 533.1; m/z found, 534.2 [M+H]+; 1H NMR (600 MHz, CD3OD) δ ppm 8.96 (d, J=0.9 Hz, 1H), 8.19 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.70 (dd, J=8.8, 2.2 Hz, 1H), 7.48-7.44 (m, 4H), 7.43-7.39 (m, 3H), 7.36-7.33 (m, 2H), 6.90 (d, J=1.6 Hz, 1H), 4.59-4.54 (m, 2H), 3.70 (s, 3H), 3.68-3.63 (m, 2H), 3.25 (s, 3H).

Provenance & Evidence