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

HRID 1524419Notes

Reaction equation

HRID 1524419 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([O:11][CH3:12])[CH:3]=1.Br[C:14]1[C:22]2[C:17](=[CH:18][C:19]([S:23]([N:26](CC3C=CC(OC)=CC=3OC)[C:27]3[S:31][N:30]=[CH:29][N:28]=3)(=[O:25])=[O:24])=[CH:20][CH:21]=2)[N:16]([CH3:43])[CH:15]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].FC(F)(F)C(O)=O>O1CCOCC1.O.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([S:23]([NH:26][C:27]4[S:31][N:30]=[CH:29][N:28]=4)(=[O:24])=[O:25])=[CH:20][CH:21]=3)[N:16]([CH3:43])[CH:15]=2)=[C:4]([O:11][CH3:12])[CH:3]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 62657Potassium Phosphate, TribasicHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 712592223-Bromo-N-(2,4-Dimethoxybenzyl)-1-Methyl-N-(1,2,4-Thiadiazol-5-yl)-1H-Indole-6-Sulfonamide2×

Product 1

HCID 712594163-(4-fluoro-2-methoxyphenyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-c44202e275e740e99770c30d0161e02d
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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