3-(Piperidin-3-YL)-1H-indole → 3-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide

HRID 2357483Notes

Reaction equation

HRID 2357483 reaction equation
C1([O:7][C:8](=O)[NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([N:23]([CH3:25])[CH3:24])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)C=CC=CC=1.[NH:27]1[CH2:32][CH2:31][CH2:30][CH:29]([C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[NH:35][CH:34]=2)[CH2:28]1>O1CCOCC1>[CH3:25][N:23]([CH3:24])[C:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:8]([N:27]2[CH2:32][CH2:31][CH2:30][CH:29]([C:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[NH:35][CH:34]=3)[CH2:28]2)=[O:7])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 153894433-(Piperidin-3-YL)-1H-indoleHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 593855643-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amideYield 31%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (529 mg, 1.5 mmole) was added to a solution of 3-piperidine-3-yl-1H-indole (300 mg, 1.5 mmole) in dioxane (10 ml). The reaction mixture was then boiled under reflux for 20 hours. The reaction mixture was worked up by distilling off the solvent. The residue contained, in addition to phenol, also the two diastereoisomers of 3-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (50 g). Methanol/EE (1:1; 900 ml) was used as eluent. The non-polar diastereoisomer of 3-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (220.6 mg, m.p. 165°-170° C., 32%) and the polar diastereoisomer of 3-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (142 mg, m.p. 95°-99° C., 31%) were thereby obtained in pure form.

Workup

  1. temperatureunder reflux for 20 hours
  2. distillationby distilling off the solvent
  3. additionThe residue contained, in addition to phenol
  4. customThe diastereoisomers were separated
  5. custompurified by flash chromatography on silica gel (50 g)

Sources & evidence

ORD record
ord-3fa1b61ed231483b9dbfb4131414128a
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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