Reaction Steps
A vial was charged with 1-(2-bromo-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (42.16 mg, 0.083 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine (27.7 mg, 0.124 mmol) Pd(AmPhos)2Cl2 (2.93 mg, 4.14 μmol), potassium phosphate (52.7 mg, 0.248 mmol), dioxane (414 μl), and water (138 μl). The vial was sealed and heated in a microwave reactor for 30 min at 100° C. The mixture was extracted with EtOAc (three times). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel, eluting with 5 to 10% MeOH/DCM, then with 15% MeOH/EtOAc, and finally with a solution of 20% of 2N ammonia in methanol in DCM. The fractions containing product were collected and concentrated. The residue was dissolved in DCM and filtered through cotton. The filtrate was concentrated to give 1-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (41.4 mg, 0.079 mmol) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=8.63 (d, J=5.7 Hz, 1H), 8.55 (d, J=1.5 Hz, 1H), 8.35 (s, 1H), 8.08 (d, J=5.8 Hz, 1H), 8.01 (d, J=6.2 Hz, 1H), 7.91 (dd, J=1.8, 8.9 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.76 (s, 1H), 7.63 (dd, J=8.4, 19.4 Hz, 2H), 6.72 (d, J=6.2 Hz, 1H), 5.37 (br. s., 1H), 2.98 (br. s., 2H), 2.52 (br. s., 2H), 2.20 (s, 3H), 2.16-1.96 (m, 2H). m/z (ESI) 526.2 (M+H)+.
