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

HRID 2357467Notes

Reaction equation

HRID 2357467 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][CH2:39][NH: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:38]2[CH2:39][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]2)=[O:25])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 548571105-chloro-3-piperidine-3-yl-1H-indoleHCID 67531726(4-Dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester

Product 1

HCID 593855653-(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 polar diastereoisomer of (4-dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester (288 mg, 0.85 mmole) was added to a solution of 5-chloro-3-piperidine-3-yl-1H-indole (200 mg, 0.85 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 (3×15 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The polar diastereoisomer of 3-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was purified by column chromatography with methanol. It was obtained in a yield of 86 mg (21%) 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 (3×15 ml)
  5. dry with materialThe organic phase was dried with Na2SO4
  6. concentrationconcentrated by evaporation
  7. customThe polar diastereoisomer of 3-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was purified by column chromatography with methanol
  8. customIt was obtained in a yield of 86 mg (21%) as a colourless solid

Sources & evidence

ORD record
ord-cdccf13ae2b9472c8ab06fec0ec23f72
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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