Potassium Phosphate, Tribasic → HCID 86687639, compound

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-(4-chloro-5-fluoro-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (INTERMEDIATE HHHHH; 80.29 mg, 0.178 mmol), (3-fluorophenyl)boronic acid (49.8 mg, 0.356 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.828 mg, 4.45 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (6.74 mg, 8.90 μmol), and potassium phosphate (113 mg, 0.534 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (809 μl) and water (81 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h at 120° C. The mixture was extracted with EtOAc (3×). The aq. layer was acidified with 0.5N aq. HCl, then extracted with EtOAc (2×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-7.5% MeOH/DCM) to give 1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (58.84 mg, 0.115 mmol, 64.7% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=14.50 (br. s., 1H), 8.79 (s, 1H), 8.71 (d, J=5.8 Hz, 1H), 8.57 (d, J=1.8 Hz, 1H), 8.14 (d, J=5.4 Hz, 1H), 7.94-7.88 (m, 1H), 7.85-7.78 (m, 1H), 7.64-7.53 (m, 3H), 7.42-7.27 (m, 3H), 3.72 (s, 3H). m/z (ESI) 511.2 (M+H)+.

Provenance & Evidence