Indole → HCID 9982498, compound

HRID 2357456Notes

Reaction equation

HRID 2357456 reaction equation
O[N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2N=N1.[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17]C=2)[CH:13]=[CH:12]1.CN1CCOCC1.[CH3:27][N:28]([CH3:45])[C:29]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:34][CH2:33][C:32](=[CH:35][C:36]([OH:38])=O)[CH2:31][CH2:30]1.C(NC1CCCCC1)(NC1CCCCC1)=O>CN(C)C=O>[CH3:45][N:28]([CH3:27])[C:29]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:30][CH2:31][C:32](=[CH:35][C:36]([N:11]2[CH2:12][CH2:13][CH:15]([C:16]3[C:5]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[NH:2][CH:17]=3)[CH2:14][CH2:19]2)=[O:38])[CH2:33][CH2:34]1

Participants

7

Reactant 5

HCID 798IndoleHCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 574382874-Dimethylamino-4-phenylcyclohexylidene-acetic acid

Product 1

HCID 9982498HCID 9982498, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-hydroxybenzotriazole (540 mg, 4.0 mmole), 3-piperidine-4-yl)-1H-indole (400 mg, 2.0 mmole) and N-methylmorpholine (0.444 ml, 4.0 mmole) were added in succession under argon to a solution of (4-dimethylamino-4-phenylcyclohexylidene)-acetic acid (592 mg, 2.0 mmole) in dry dimethylformamide (10 ml). The solution was cooled in an ice bath and dicyclohexyldicarbodiimide (826 g, 4.0 mmole) was added. The reaction mixture was stirred for 4 days at RT, the dicyclohexylurea precipitating out little by little. The reaction mixture was worked up by separating the precipitated urea and adding the filtrate to a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Oily products thereupon precipitated out, which could not be separated by filtration. The reaction mixture was extracted with DCM (3×70 ml), the extracts were combined and the organic phase was washed with water (2×50 ml). After drying, the organic phase was concentrated by evaporation, 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[4-(1H-indol-3-yl)-piperidine-1-yl]-ethanone being obtained as a brown, oily crude product. After chromatographic separation on silica gel (70 g) with EE/methanol (2:1), 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[4-(1H-indol-3-yl)-piperidine-1-yl]-ethanone was isolated as a yellow foamy solid in a yield of 41% (359 mg).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. customby separating the precipitated urea
  3. additionadding the filtrate
  4. additionto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customOily products thereupon precipitated out
  6. customwhich could not be separated by filtration
  7. extractionThe reaction mixture was extracted with DCM (3×70 ml)
  8. washthe organic phase was washed with water (2×50 ml)
  9. customAfter drying
  10. concentrationthe organic phase was concentrated by evaporation, 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[4-(1H-indol-3-yl)-piperidine-1-yl]-ethanone being
  11. customobtained as a brown, oily crude product
  12. customAfter chromatographic separation on silica gel (70 g) with EE/methanol (2:1)

Sources & evidence

ORD record
ord-6c3329fbb04b47f8a3cbe5d3c908be9b
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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