Ammonium Chloride → 2'-Fluoro-5'-[7-(1-hydroxy-1-methylethyl)-[1,8]naphthyridin-4-yl]biphenyl-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5′-[7-acetyl-[1,8]naphthyridin-4-yl]-2′-fluorobiphenyl-2-carbonitrile (from Example 58) (28.6 mg, 0.0778 mmol) in anhydrous THF (2 mL), cooled under nitrogen to −78° C., was added dropwise methylmagnesium bromide (3.0 M solution in Et2O, 26.0 μL, 0.078 mmol). The mixture was stirred at −78° C. for a total of 85 min, adding more methylmagnesium bromide (3.0 M solution in Et2O, 26.0 μL, 0.078 mmol) after 45 min and 70 min. Saturated aqueous NH4Cl (2 mL) was then added and the mixture was allowed to warm to room temperature. The mixture was partitioned between ethyl acetate (15 mL) and water (10 mL). The aqueous layer was extracted further with ethyl acetate (15 mL), and the combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 3% MeOH/CH2Cl2, to afford 20.6 mg (69%) of the title compound as a white solid. δH (360 MHz, CDCl3) 1.67 (6H, s), 5.32 (1H, s), 7.44 (1H, t, J 9.1), 7.51 (1H, d, J 4.6), 7.54 (1H, td, J 7.7, 1.1), 7.58-7.65 (4H, m), 7.71 (1H, td, J 7.7, 1.1), 7.84 (1H, dd, J 7.7, 1.1), 8.51 (1H, d, J 8.8), 9.15 (1H, d, J 4.2). m/z (ES+) 384 [MH]+.

Provenance & Evidence