To a vial containing 4-fluoro-2-methoxyphenylboronic acid (0.075 g, 0.450 mmol) was added a solution of 3-bromo-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (Intermediate D) (0.100 g, 0.191 mmol) and Pd(AmPhos)2Cl2 (0.014 g, 0.019 mmol) in 1 mL of dioxane. A solution of tripotassium phosphate (0.142 g, 0.669 mmol) in 318 μL of water was added, and the vial was sealed and placed in a heated shaker block. The vial was shaken for 2 hours at 100° C. The vial was uncapped and the reaction was concentrated. The resulting solid was dissolved in a solution of trifluoroacetic acid (0.293 mL, 3.82 mmol) in 1 mL of dichloromethane. The reaction was shaken at room temperature for 1 hour. The solution was filtered and the solids were washed with DCM and methanol. The filtrate was concentrated and purified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier) to afford 3-(4-fluoro-2-methoxyphenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.79 (s, 3 H) 3.87 (s, 3 H) 6.83 (td, J=8.42, 2.52 Hz, 1 H) 7.01 (d, J=2.52 Hz, 1 H) 6.99 (d, J=2.52 Hz, 1 H) 7.43-7.48 (m, 2 H) 7.56 (d, J=8.48 Hz, 1 H) 7.65 (s, 1 H) 7.84-7.90 (m, 2 H). m/z (ESI) 418.1 (M+H)+.
