Diethyl Ether → 2-(4-Piperazin-1-yl-benzenesulfonyl)-1H-indole

HRID 1793871Notes

Reaction equation

HRID 1793871 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[S:17]([C:20]1[CH:25]=[CH:24][C:23](F)=[CH:22][CH:21]=1)(=[O:19])=[O:18])=O)(C)(C)C.[NH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(OCC)C.CCCCCC>C(OCC)(=O)C>[N:27]1([C:23]2[CH:22]=[CH:21][C:20]([S:17]([C:9]3[NH:8][C:16]4[C:11]([CH:10]=3)=[CH:12][CH:13]=[CH:14][CH:15]=4)(=[O:18])=[O:19])=[CH:25][CH:24]=2)[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 4837PiperazineHCID 8058HexaneHCID 21021922HCID 21021922, compound

Product 1

HCID 103599742-(4-Piperazin-1-yl-benzenesulfonyl)-1H-indoleYield 31.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The Boc-protecting group on 0.530 g, 1.41 mmol of the 2-(4-Fluorobenzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester from Step 1 was removed by stirring at room temperature in 3 mL of neat TFA. The reaction mixture turned a light burgundy color while stirring. The TFA was removed by adding 25 mL of toluene and removing the solvent/TFA as an azeotrope. This was repeated and the oily residue was then transferred to a sealed tube using 5 mL of DMSO. Solid piperazine (0.61 g, 7.06 mmol, 5 eq.) was added, the tube was sealed, and the reaction mixture heated at 100° C. (bath temp.) for a period of 16 h. The reaction mixture was allowed to cool to room temperature, diluted with 400 mL of ethyl acetate, then washed sequentially with saturated NaHCO3 solution, water, brine, and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave an amber glass which was treated with anhydrous diethyl ether. Hexane (25 mL) was added to the solution, causing a small amount of solid to precipitate out of solution. The mixture cooled was to 0° C. in an ice-water bath, followed by vacuum-filtration of the off-white solid. After drying, 0.150 g, 0.44 mmol, 31.1% yield of 2-(4-Piperazin-1-yl-benzenesulfonyl)-1H-indole was obtained, with a melting point range of 246–248.5° C. and M+H of 342.

Workup

  1. customwas removed
  2. stirringwhile stirring
  3. customThe TFA was removed
  4. additionby adding 25 mL of toluene
  5. customremoving the solvent/TFA as an azeotrope
  6. customthe oily residue was then transferred to a sealed tube
  7. customthe tube was sealed
  8. temperaturethe reaction mixture heated at 100° C. (bath temp.) for a period of 16 h
  9. temperatureto cool to room temperature
  10. washwashed sequentially with saturated NaHCO3 solution, water, brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customEvaporation of the solvent
  13. customgave an amber glass which
  14. customto precipitate out of solution
  15. temperatureThe mixture cooled
  16. customwas to 0° C. in an ice-water bath
  17. filtrationfollowed by vacuum-filtration of the off-white solid
  18. customAfter drying

Sources & evidence

ORD record
ord-a1fb158f297546f09c9fb1d3654d2cd4
Source dataset
uspto-grants-2006_04
Patent number
US07022708B2

Reaction notes

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