3-(4-Piperidinyl)-1H-indole → HCID 10416821, compound

HRID 2357447Notes

Reaction equation

HRID 2357447 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][CH:30]([C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[NH:35][CH:34]=2)[CH2:29][CH2:28]1>O1CCOCC1>[CH3:24][N:23]([CH3:25])[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][CH:30]([C:33]3[C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[NH:35][CH:34]=3)[CH2:29][CH2:28]2)=[O:7])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 7022353-(4-Piperidinyl)-1H-indoleHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 10416821HCID 10416821, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (599 mg, 1.7 mmole) was added to a solution of 3-piperidine-4-yl-1H-indole (340.5 mg, 1.7 mmole) in dioxane (12 ml). The reaction mixture was a clear solution above 40° C., and this solution was boiled for 24 hours under reflux. No precipitate was formed even at RT. The solvent was distilled off in vacuo. The residue contained, besides phenol, the two diastereoisomers of 4-(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 (75 g). Methanol/EE (1:1; 800 ml) and methanol (500 ml) were used as eluent. The non-polar diastereoisomer (281 mg, m.p. 89°-93° C., 36%) and the polar diastereoisomer of 4-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (262 mg, m.p. 104°-107° C., 34%) were thereby obtained in pure form.

Workup

  1. customa clear solution above 40° C.
  2. temperatureunder reflux
  3. customNo precipitate was formed even at RT
  4. distillationThe solvent was distilled off in vacuo
  5. customThe diastereoisomers were separated
  6. custompurified by flash chromatography on silica gel (75 g)

Sources & evidence

ORD record
ord-8de6295d266d4effbfc834e05b571ac2
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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