(3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone → (3-(Benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanol

Participants

Reaction Steps

LaCl3-2LiCl (0.6 M in THF, 0.78 mL, 0.47 mmol) was added dropwise by syringe to a solution of (3-(benzo[b]thiophen-2-ylmethyl)-4-chloro-2-methoxyquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (101.4 mg, 0.226 mmol, Intermediate 40: step b) in dry THF (2 mL). After 5 minutes, the solution was cooled in an ice bath and pyridin-2-ylmagnesium bromide (2.8 mL, 0.7 mmol) was added dropwise via syringe. The reaction was stirred for 3 hours, then quenched with saturated aqueous ammonium chloride and removed from the cold bath. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography (silica gel, 0-5% MeOH-DCM) followed by reverse-phase chromatography (acetonitrile/H2O+0.05% TFA). The isolated product fractions were basified with saturated aqueous sodium bicarbonate, extracted with DCM, dried (Na2SO4), filtered, and concentrated to dryness to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.63-8.59 (m, 1H), 8.13 (d, J=2.0 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.71-7.60 (m, 4H), 7.49 (d, J=1.1 Hz, 1H), 7.30-7.18 (m, 4H), 7.08 (d, J=1.0 Hz, 1H), 6.32 (d, J=1.1 Hz, 1H), 4.50 (d, J=1.1 Hz, 2H), 4.13 (s, 3H), 3.41 (s, 3H); MS m/e 527.2 [M+H]+.

Provenance & Evidence