Potassium Phosphate, Tribasic → HCID 86687630, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-(4-chloro-2-methylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (EXAMPLE 357; 61.66 mg, 0.150 mmol) (3-fluorophenyl)boronic acid (42.0 mg, 0.300 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (3.08 mg, 7.50 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (11.37 mg, 0.015 mmol) and potassium phosphate (96 mg, 0.450 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (682 μl) and water (68.2 μl) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h 45 min at 100° C. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3% MeOH/DCM) to give 1-(3′-fluoro-3-methyl-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (29.49 mg, 0.063 mmol, 41.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.08 (br. s., 1H), 8.77-8.67 (m, 2H), 8.58 (s, 1H), 8.24 (br. s., 1H), 8.15 (d, J=5.6 Hz, 1H), 7.98 (dd, J=1.8, 8.9 Hz, 1H), 7.80-7.72 (m, 2H), 7.71-7.61 (m, 3H), 7.55 (dt, J=6.2, 8.0 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.28-7.19 (m, 1H), 7.03 (br. s., 1H), 2.06 (s, 3H). m/z (ESI) 471.2 (M+H)+.

Provenance & Evidence