Potassium Phosphate, Tribasic → perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate

HRID 1524387Notes

Reaction equation

HRID 1524387 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([S:11]([O:14][C:15]3[C:20]([F:21])=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:16]=3[F:25])(=[O:13])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH3:26])[CH:3]=1.[CH3:27][N:28]1[C:32]([C:33]2[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:34]=2B(O)O)=[CH:31][CH:30]=[N:29]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.O1CCOCC1>[CH3:26][N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([S:11]([O:14][C:15]3[C:20]([F:21])=[C:19]([F:22])[C:18]([F:23])=[C:17]([F:24])[C:16]=3[F:25])(=[O:13])=[O:12])[CH:6]=2)[C:2]([C:34]2[CH:35]=[CH:36][C:37]([C:39]([F:42])([F:40])[F:41])=[CH:38][C:33]=2[C:32]2[N:28]([CH3:27])[N:29]=[CH:30][CH:31]=2)=[CH:3]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, Tribasic2×HCID 71258947(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid3×HCID 89407702perfluorophenyl 3-bromo-1-methyl-1H-indole-6-sulfonate2×

Product 1

HCID 89407674perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonateYield 364.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

The following reaction was conducted in two separate vials, and the reaction mixtures were combined before purification: A vial was charged with perfluorophenyl 3-bromo-1-methyl-1H-indole-6-sulfonate (52.1 mg, 0.114 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (Intermediate G) (40.1 mg, 0.148 mmol), potassium phosphate (72.7 mg, 0.343 mmol), Pd(AmPhos)2Cl2 (4.04 mg, 5.71 μmol), 1,4-dioxane (428 μl), and water (143 μl). The vial was flushed with Ar, sealed, and heated in a microwave reactor to 90° C. for 30 min. A separate vial was charged with perfluorophenyl 3-bromo-1-methyl-1H-indole-6-sulfonate (180 mg, 0.395 mmol), (2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)boronic acid (139 mg, 0.513 mmol), potassium phosphate (251 mg, 1.184 mmol), Pd(AmPhos)2Cl2 (13.97 mg, 0.020 mmol), 1,4-dioxane (1480 μl), and water (493 μl). The vial was flushed with Ar, sealed, and heated in a reactor to 90° C. for 30 min. The reaction mixtures from both vials were combined, and the combined mixture was diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (10 to 60% EtOAc/Heptane) to give perfluorophenyl 1-methyl-3-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-1H-indole-6-sulfonate (250.0 mg, 0.416 mmol, 82% yield) as a pink foam. 1H NMR (400 MHz, CDCl3) δ=8.09-8.01 (m, 1 H), 7.91-7.81 (m, 3 H), 7.76-7.67 (m, 2 H), 7.53 (d, J=2.0 Hz, 1 H), 6.79 (s, 1 H), 6.38 (d, J=1.9 Hz, 1 H), 3.81 (s, 3 H), 3.23 (s, 3 H). m/z (ESI) 602.0 (M+H)+.

Workup

  1. customThe following reaction
  2. customseparate vials
  3. customthe reaction mixtures
  4. customwere combined before purification
  5. customThe vial was flushed with Ar
  6. customsealed
  7. customThe vial was flushed with Ar
  8. customsealed
  9. temperatureheated in a reactor to 90° C. for 30 min
  10. additionthe combined mixture was diluted with water
  11. extractionextracted with EtOAc (2×)
  12. dry with materialThe combined organic extracts were dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product was purified by chromatography on silica gel (10 to 60% EtOAc/Heptane)

Sources & evidence

ORD record
ord-23291defe4274681a5bd90a6ea949912
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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