Potassium Carbonate → 4-(3'-fluoro-4-methoxy-[1,1'-biphenyl]-3-yl)-N-(pyrimidin-4-yl)quinoline-7-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 4-chloro-N-(pyrimidin-4-yl)quinoline-7-sulfonamide (INTERMEDIATE OOOO, 103.75 mg, 0.323 mmol), (2-chlorophenyl)boronic acid (53.1 mg, 0.340 mmol), potassium carbonate (134 mg, 0.970 mmol), and Pd(Ph3P)4 (18.69 mg, 0.016 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (1213 μl) and water (404 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h at 100° C. LCMS showed about 5% starting material remaining. (3-fluorophenyl)boronic acid (100 mg, 0.712 mmol), S-Phos Precatalyst (Strem Chemical, Newburyport, Mass., 24.50 mg, 0.032 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (6.64 mg, 0.016 mmol), and potassium phosphate (206 mg, 0.970 mmol) were added. The vial was heated in the microwave at 100° C. for 1 h. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (25-g Interchim 15-micron column, 3.5% MeOH/DCM). Several mixed fractions were discarded. Those fractions containing clean product were combined and concentrated to give 4-(3′-fluoro-4-methoxy-[1,1′-biphenyl]-3-yl)-N-(pyrimidin-4-yl)quinoline-7-sulfonamide (22 mg, 0.045 mmol, 13.98% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.30-12.39 (m, 1H), 9.13-9.07 (m, 1H), 8.63-8.53 (m, 2H), 8.28 (d, J=5.4 Hz, 1H), 7.93 (ddd, J=2.2, 8.8, 17.8 Hz, 2H), 7.74 (d, J=8.8 Hz, 1H), 7.69-7.62 (m, 2H), 7.59-7.52 (m, 2H), 7.50-7.41 (m, 1H), 7.34 (d, J=8.7 Hz, 1H), 7.17-7.11 (m, 1H), 7.06 (d, J=5.5 Hz, 1H), 3.72 (s, 3H). m/z (ESI) 487.2 (M+H)+.

Provenance & Evidence