4-Bromo-2,6-dichlorobenzene-1-sulfonyl chloride → 4-Bromo-2,6-dichloro-N-[2,2,2-trifluoro-1-(1H-indol-3-ylmethyl)ethyl]benzenesulfonamide

HRID 1868407Notes

Reaction equation

HRID 1868407 reaction equation
[F:1][C:2]([F:16])([F:15])[CH:3]([NH2:14])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.[Br:17][C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([S:25](Cl)(=[O:27])=[O:26])=[C:20]([Cl:29])[CH:19]=1>N1C=CC=CC=1.Cl.C(OCC)(=O)C>[Br:17][C:18]1[CH:23]=[C:22]([Cl:24])[C:21]([S:25]([NH:14][CH:3]([CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][CH:6]=2)[C:2]([F:1])([F:15])[F:16])(=[O:26])=[O:27])=[C:20]([Cl:29])[CH:19]=1

Participants

6

Reactant 2

HCID 27374664-Bromo-2,6-dichlorobenzene-1-sulfonyl chlorideHCID 539884361,1,1-trifluoro-3-(1H-indol-3-yl)propan-2-amine

Product 1

HCID 116564904-Bromo-2,6-dichloro-N-[2,2,2-trifluoro-1-(1H-indol-3-ylmethyl)ethyl]benzenesulfonamideYield 30%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 170 mg (0.75 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-ylmethyl)ethylamine and 243 mg (0.75 mmol) of 4-bromo-2,6-dichlorobenzensulfonyl chloride in 4 mL of pyridine was warmed at 65° C. The reaction was monitored by TLC indicating a new less polar product compared to amine. After 16 hours, the mixture was cooled and concentrated to afford a thick oily residue. The residue was diluted with 1 N aqueous hydrochloric acid until acidic and extracted with ethyl acetate. The combined organic layers were washed with 1 N aqueous HCl, saturated aqueous sodium bicarbonate solution, and brine, dried over sodium sulfate, decanted, and concentrated in vacuo. The crude material was purified by preparative TLC using EtOAc-hexanes (15:85). Material from the preparative TLC was isolated by suspending the silica gel in ethyl acetate followed by filtration. The filtrate was concentrated in vacuo to afford 112 mg (30%) of the title compounds as an off-white crystalline solid.

Workup

  1. temperaturethe mixture was cooled
  2. concentrationconcentrated
  3. customto afford a thick oily residue
  4. extractionextracted with ethyl acetate
  5. washThe combined organic layers were washed with 1 N aqueous HCl, saturated aqueous sodium bicarbonate solution, and brine
  6. dry with materialdried over sodium sulfate
  7. customdecanted
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by preparative TLC
  10. customMaterial from the preparative TLC was isolated
  11. filtrationfollowed by filtration
  12. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-3a17734b5c7349628347b788cd5ac8fe
Source dataset
uspto-grants-2009_12
Patent number
US07635711B2

Reaction notes

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