Cesium carbonate → 6-(4-Methyl-piperazin-1-yl)-1-(toluene-4-sulfonyl)-1H-indole

HRID 1465832Notes

Reaction equation

HRID 1465832 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(OC1C=CC=C(OC(C)C)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1)C.[CH3:60][N:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:60][N:61]1[CH2:66][CH2:65][N:64]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[CH:7][N:8]3[S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[CH:4][CH:3]=2)[CH2:63][CH2:62]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 11348662HCID 11348662, compoundHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl

Product 1

HCID 674572186-(4-Methyl-piperazin-1-yl)-1-(toluene-4-sulfonyl)-1H-indoleYield 73.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A 250 mL round bottom flask was loaded with 6-Bromo-1-(toluene-4-sulfonyl)-1H-indole (4 g, 11.4 mmol), Cs2CO3 (7.4 g, 22.8 mmol), Pd2dba3 (0.104 g, 0.114 mmol), RuPHOS (0.106 g, 0.23 mmol), Toluene (150 mL), N-Methyl piperazine (1.9 mL, 17.2 mol), evacuated and flushed with nitrogen. Next the reaction flask was heated at 100° C., over the weekend. Analysis at this point showed that most of the starting material had converted to the product. After cooling to room temperature, the solution was diluted with EtOAc (150 mL), filtered through a pad of celite, washed with additional EtOAc (150 mL) and was evaporated. The resulting oil was chromatographed on silica gel to give the product as a thick brown oil (which crystallized on standing), 3.1 g, (73.8% yield).

Workup

  1. customevacuated
  2. customflushed with nitrogen
  3. temperatureAfter cooling to room temperature
  4. additionthe solution was diluted with EtOAc (150 mL)
  5. filtrationfiltered through a pad of celite
  6. washwashed with additional EtOAc (150 mL)
  7. customwas evaporated
  8. customThe resulting oil was chromatographed on silica gel

Sources & evidence

ORD record
ord-ccba6e2f6fbc48ddbacfb2035fa5d78f
Source dataset
uspto-grants-2015_04
Patent number
US08999993B2

Reaction notes

Loading…