Potassium Phosphate, Tribasic → HCID 86687640, 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; 74.29 mg, 0.165 mmol) pyridin-3-ylboronic acid (24.30 mg, 0.198 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (1.691 mg, 4.12 μmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (6.24 mg, 8.24 μmol) and potassium phosphate (105 mg, 0.494 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (749 μl) and water (74.9 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 (4×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 0-10% MeOH/DCM) to give 1-(5-fluoro-2-methoxy-4-(pyridin-3-yl)phenyl)-N-(1,3,4-thiadiazol-2-yl)isoquinoline-6-sulfonamide (49.13 mg, 0.100 mmol, 60.4% yield) as a light-yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=14.53 (br. s., 1H), 8.93 (s, 1H), 8.78 (s, 1H), 8.71 (d, J=5.7 Hz, 1H), 8.67 (dd, J=1.3, 4.7 Hz, 1H), 8.57 (d, J=1.7 Hz, 1H), 8.14 (d, J=5.8 Hz, 2H), 7.96-7.87 (m, 1H), 7.86-7.78 (m, 1H), 7.63-7.54 (m, 1H), 7.45-7.36 (m, 2H), 3.73 (s, 3H). m/z (ESI) 494.1 (M+H)+.

Provenance & Evidence