4-(5-chloro-[1H]-indol-3-yl)-piperidine → 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide

HRID 2357462Notes

Reaction equation

HRID 2357462 reaction equation
C1(O[C:8](=[O:25])[NH:9][CH:10]2[CH2:15][CH2:14][C:13]([N:22]([CH3:24])[CH3:23])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)C=CC=CC=1.[Cl:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1>O1CCOCC1>[CH3:24][N:22]([CH3:23])[C:13]1([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11][CH:10]([NH:9][C:8]([N:39]2[CH2:40][CH2:41][CH:36]([C:30]3[C:29]4[C:33](=[CH:34][CH:35]=[C:27]([Cl:26])[CH:28]=4)[NH:32][CH:31]=3)[CH2:37][CH2:38]2)=[O:25])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 128313754-(5-chloro-[1H]-indol-3-yl)-piperidineHCID 67531726(4-Dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester

Product 1

HCID 117562474-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The non-polar diastereoisomer of (4-dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester (338 mg, 1.0 mmole) was added to a solution of 5-chloro-3-piperidine-4-yl-1H-indole (218 mg, 1.0 mmole) in dioxane (10 ml). The reaction mixture was then boiled under reflux for 32 hours. The reaction mixture was worked up by distilling off dioxane and diluting with water (10 ml). The reaction mixture was adjusted to pH 11 with 5M NaOH and extracted with EE (3×20 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The non-polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was recrystallised from methanol (5 ml). It was obtained in a yield of 120 mg (25%) as a colourless solid.

Workup

  1. temperatureunder reflux for 32 hours
  2. distillationby distilling off dioxane
  3. additiondiluting with water (10 ml)
  4. extractionextracted with EE (3×20 ml)
  5. dry with materialThe organic phase was dried with Na2SO4
  6. concentrationconcentrated by evaporation
  7. customThe non-polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was recrystallised from methanol (5 ml)
  8. customIt was obtained in a yield of 120 mg (25%) as a colourless solid

Sources & evidence

ORD record
ord-f82e82bd937949ffaa1b6c68fcf35db4
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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