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

HRID 2357463Notes

Reaction equation

HRID 2357463 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.[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH:32]=[C:31]2[CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]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:40]2[CH2:41][CH2:42][CH:37]([C:31]3[C:30]4[C:34](=[CH:35][CH:36]=[C:28]([O:27][CH3:26])[CH:29]=4)[NH:33][CH:32]=3)[CH2:38][CH2:39]2)=[O:25])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 432245-Methoxy-3-(piperidin-4-yl)-1H-indoleHCID 67531726(4-Dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester

Product 1

HCID 102557934-(5-methoxy-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-methoxy-3-piperidine-4-yl-1H-indole (230 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-methoxy-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 170 mg (36%) 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-methoxy-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 170 mg (36%) as a colourless solid

Sources & evidence

ORD record
ord-7b3c39a42827404a9c213a100f490995
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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