Trifluoroacetic acid → 3-(4-fluoro-2-methoxyphenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Temperature

100 °C

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)+.

1. customthe vial was sealed
2. concentrationthe reaction was concentrated
3. stirringThe reaction was shaken at room temperature for 1 hour
4. filtrationThe solution was filtered
5. washthe solids were washed with DCM and methanol
6. concentrationThe filtrate was concentrated
7. custompurified via reverse phase HPLC (8 min gradient elution 15 to 75% ACN/H2O, 0.1% TFA modifier)

ORD record

ord-c44202e275e740e99770c30d0161e02d

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079902B2