N,N'-Dimethylethylenediamine → HCID 10015826, compound

HRID 2212983Notes

Reaction equation

HRID 2212983 reaction equation
[CH3:1][NH:2]CCNC.I[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[C@@H:17]1[CH2:21][CH2:20][CH2:19][C@H:18]1[CH2:22][N:23]([CH3:25])[CH3:24].[C-]#N.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Cu]I>[CH3:24][N:23]([CH2:22][C@@H:18]1[CH2:19][CH2:20][CH2:21][C@H:17]1[C:11]1[C:10]2[C:14](=[CH:15][CH:16]=[C:8]([C:1]#[N:2])[CH:9]=2)[NH:13][CH:12]=1)[CH3:25]

Participants

7

Reactant 3

HCID 8070N,N'-DimethylethylenediamineHCID 8929Sodium CyanideHCID 86591648HCID 86591648, compound

Product 1

HCID 10015826HCID 10015826, compoundYield 83%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
125 °C

Procedure

N,N′-dimethylethylenediamine (5.66 mL, 53 mMol) was added to a mixture of trans [2-(5-iodo-1H-indol-3-yl)-cyclopentylmethyl]-dimethylamine (19.4 g, 53 mMol), sodium cyanide (3.1 g, 63 mMol), and copper(I) iodide (1 g, 5.3 mMol) in deoxygenated anhydrous toluene (50 mL). The resulting mixture was heated in an oil bath to 125° C. under N2 for ˜18 h. The reaction was cooled to 50° C., diluted with ethyl acetate (400 mL), and heated to reflux for 5 min. The resulting suspension was transferred to a separatory funnel and washed with aqueous NaHCO3 (400 mL and twice with 200 mL). Every aqueous layer was extracted with ethyl acetate (50 mL) to make sure no product was left in aqueous layer. The combined organic layers were dried over MgSO4. Solvent was removed in vacuo to give the crude product which was purified by silica gel chromatography using dichloromethane/2.0 M ammonia in methanol (100/0 to 93/7) as the eluent, to give trans 3-(2-dimethylaminomethyl-cyclopentyl)-1H-indole-5-carbonitrile (11.7 g, 83%).

Workup

  1. temperatureThe reaction was cooled to 50° C.
  2. temperatureheated
  3. temperatureto reflux for 5 min
  4. customThe resulting suspension was transferred to a separatory funnel
  5. washwashed with aqueous NaHCO3 (400 mL
  6. extractionEvery aqueous layer was extracted with ethyl acetate (50 mL)
  7. waitwas left in aqueous layer
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. customSolvent was removed in vacuo
  10. customto give the crude product which
  11. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-0a78df90baae4bed859b8042bea18d19
Source dataset
uspto-grants-2006_09
Patent number
US07105516B2

Reaction notes

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