Reaction Steps
A solution of Cl2Pd(AmPhos) (Sigma-Aldrich, St. Louis, Mo., 0.136 g, 0.193 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Frontier Scientific, Logan, Utah, 1.191 g, 3.85 mmol), 5-(2-bromo-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide (Example 4, 1.000 g, 1.925 mmol), and potassium phosphate (1.635 g, 7.70 mmol) in 20 mL dioxane, 10 mL water was heated to 120° C. for 2 hours. The reaction mixture was diluted with EtOAc and washed with 1 N citric acid solution. The organics were dried over MgSO4 and concentrated. Purification of the resulting residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave tert-butyl 4-(2-(2-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (0.635 g, 1.021 mmol). [M+H]+=522.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 8.28 (s, 1H), 7.63-7.70 (m, 2H), 7.43 (d, J=7.8 Hz, 1H), 7.15-7.30 (m, 2H), 7.07 (d, J=7.4 Hz, 1H), 5.72 (s, 1H), 4.31-4.44 (m, 2H), 3.87 (br. s., 2H), 3.41-3.48 (m, 1H), 3.16-3.36 (m, 1H), 2.78 (br. s., 4H), 2.69 (m, 1H), 2.48-2.55 (m, 1H), 1.37-1.47 (m, 9H)
