N,N'-Dimethylethylenediamine → 1-(4-Methylbenzene-1-sulfonyl)-1H-indole-5-carbonitrile

HRID 2253497Notes

Reaction equation

HRID 2253497 reaction equation
[C-]#N.[Na+].Br[C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[CH:9]=[CH:8]2.[CH3:24][NH:25]CCNC.[OH-].[NH4+]>[Cu]I.O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[C:20]1([CH3:23])[CH:21]=[CH:22][C:17]([S:14]([N:10]2[C:11]3[C:7](=[CH:6][C:5]([C:24]#[N:25])=[CH:13][CH:12]=3)[CH:8]=[CH:9]2)(=[O:16])=[O:15])=[CH:18][CH:19]=1

Participants

9

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 8929Sodium CyanideHCID 14923Ammonium HydroxideHCID 119546185-Bromo-1-(4-methylbenzene-1-sulfonyl)-1H-indole

Product 1

HCID 224925731-(4-Methylbenzene-1-sulfonyl)-1H-indole-5-carbonitrileYield 86%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

An oven dried screw cap test tube was charged with NaCN (106 mg, 2.163 mmol), dried KI (60 mg, 0.361 mmol, 20 mol %), CuI (34 mg, 0.178 mmol, 10 mol %), 5-bromo-1-(toluene-4-sulfonyl)-1H-indole (630 mg, 1.803 mmol), evacuated and backfilled with argon three times. N,N′-dimethylethylenediamine (195 μL, 1.832 mmol) and anhydrous toluene (1.1 mL) were added under argon. The tube was sealed and the reaction mixture was stirred magnetically at 110 ° C. for 24 h. The resulting yellow suspension was cooled to room temperature, 2 mL of ethyl acetate, 1 mL of ammonium hydroxide (30%) and 1 mL of water were added. The mixture was stirred at 25° C. for 10 min, then the organic layer was separated and the aqueous layer was extracted three times with ethyl acetate (3×2 mL). The organic layers combined were washed with 5 mL of water and dried over MgSO4. The solvent was removed at reduced pressure. Purification of the residue by flash chromatography on silica gel (2×15 cm; hexane/ethyl acetate 10:1) provided 459 mg (86% yield) of the title compound as a white solid.

Workup

  1. customAn oven dried screw
  2. customcap test tube
  3. customevacuated
  4. customThe tube was sealed
  5. temperatureThe resulting yellow suspension was cooled to room temperature
  6. stirringThe mixture was stirred at 25° C. for 10 min
  7. customthe organic layer was separated
  8. extractionthe aqueous layer was extracted three times with ethyl acetate (3×2 mL)
  9. washThe organic layers combined were washed with 5 mL of water
  10. dry with materialdried over MgSO4
  11. customThe solvent was removed at reduced pressure
  12. customPurification of the residue by flash chromatography on silica gel (2×15 cm; hexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-b11fb260f7c94cdba1cd9c5fd7f88bed
Source dataset
uspto-grants-2008_01
Patent number
US07323608B2

Reaction notes

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