Water → tert-Butyl 5-(4-methylpiperazin-1-yl)-1H-indole-1-carboxylate

HRID 20990

Reaction equation

HRID 20990 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13](I)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([N:22]3[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 161259585-Iodo-1H-indole, N-BOC protected

Product 1

HCID 58117405tert-Butyl 5-(4-methylpiperazin-1-yl)-1H-indole-1-carboxylateYield 28%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

1-(tert-Butoxycarbonyl)-5-iodoindole (3.46 g, 10.1 mmol) was dissolved in toluene (45.0 mL), and the solution was added with 4-methylpiperazine (2.24 mL, 20.2 mmol), 2,2′-(diphenylphosphino)-1,1′-binaphthyl (1.26 g, 2.02 mmol), cesium carbonate (4.94 mg, 15.2 mmol) and palladium acetate (226 mg, 1.01 mmol), followed by stirring under reflux for 24 hours. The mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography (chloroform/methanol=9/1) to obtain 1-(tert-butoxycarbonyl)-5-(4-methylpiperazino)indole (887 mg, 28%).

Workup

  1. temperatureunder reflux for 24 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by flash column chromatography (chloroform/methanol=9/1)

Sources & evidence

ORD record
ord-9b5aef98020e4bc380e5b6f42844c23d
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

Loading…