Potassium Phosphate, Tribasic → HCID 86687614, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(isoxazol-3-yl)isoquinoline-6-sulfonamide (INTERMEDIATE WWWW, 95.3 mg, 0.216 mmol), (3-fluorophenyl)boronic acid (60.5 mg, 0.432 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (2.219 mg, 5.40 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (8.19 mg, 10.81 μmol), and potassium phosphate (138 mg, 0.649 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (983 μl) and water (98 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 2.5 h at 120° C. Additional portions of (3-fluorophenyl)boronic acid (60.5 mg, 0.432 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (8.19 mg, 10.81 μmol), and potassium phosphate (138 mg, 0.649 mmol) were added. The vial was heated for an additional 30 min at 150° C. The mixture organic layer was separated, and the aq. layer was diluted with 0.5 N aq. HCl and 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, 0-4% MeOH/DCM) to give a light-yellow solid. The material was taken up in DCM, sonicated, and filtered. The collected solid was washed with DCM (2×), dried under a stream of N2 (g), then dried under vacuum to give 1-(2-cyano-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(isoxazol-3-yl)isoquinoline-6-sulfonamide (22.04 mg, 0.044 mmol, 20.37% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.93 (br. s., 1H), 8.82-8.64 (m, 3H), 8.19 (d, J=5.7 Hz, 1H), 8.01-7.83 (m, 3H), 7.71-7.55 (m, 3H), 7.49-7.33 (m, 2H), 6.50 (d, J=1.7 Hz, 1H), 3.81 (s, 3H). m/z (M+H) 501.0 (M+H)+.

Provenance & Evidence