Potassium Phosphate, Tribasic → 1-(2-cyano-5-methoxy-3'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 1-(4-chloro-5-cyano-2-methoxyphenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (EXAMPLE 337, 69.8 mg, 0.152 mmol) (3-(trifluoromethyl)phenyl)boronic acid (57.9 mg, 0.305 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (3.13 mg, 7.62 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (11.55 mg, 0.015 mmol) and potassium phosphate (162 mg, 0.762 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (693 μl) and water (69.3 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, MeOH-EtOAc, and MeOH-DCM. 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 an off-white solid. The solid was taken up in DCM and filtered. The collected solid was washed with DCM (2×), dried under a stream of N2 (g), and dried under vacuum to give 1-(2-cyano-5-methoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.80 (s, 1H), 8.73 (d, J=5.7 Hz, 1H), 8.62-8.55 (m, 1H), 8.17 (d, J=5.6 Hz, 1H), 8.11-8.04 (m, 2H), 7.98 (s, 1H), 7.96-7.78 (m, 3H), 7.51 (s, 1H), 7.19 (br. s., 1H), 3.83 (s, 3H). m/z (ESI) 567.9 (M+H)+.

Provenance & Evidence