5-fluoro-3-(piperidin-3-yl)-1H-indole → 3-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide

HRID 2357485Notes

Reaction equation

HRID 2357485 reaction equation
[N+](C1C=CC(O[C:11](=[O:29])[NH:12][CH2:13][CH:14]2[CH2:19][CH2:18][C:17]([N:26]([CH3:28])[CH3:27])([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=CC=1)([O-])=O.[F:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][CH:35]=[C:34]2[CH:40]1[CH2:45][CH2:44][CH2:43][NH:42][CH2:41]1>O1CCOCC1>[CH3:28][N:26]([CH3:27])[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:18][CH2:19][CH:14]([CH2:13][NH:12][C:11]([N:42]2[CH2:43][CH2:44][CH2:45][CH:40]([C:34]3[C:33]4[C:37](=[CH:38][CH:39]=[C:31]([F:30])[CH:32]=4)[NH:36][CH:35]=3)[CH2:41]2)=[O:29])[CH2:15][CH2:16]1

Participants

4

Reactant 2

HCID 574383045-fluoro-3-(piperidin-3-yl)-1H-indoleHCID 67532180(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid 4-nitrophenyl ester

Product 1

HCID 593855623-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amideYield 25%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid 4-nitrophenyl ester (400 mg, 1 mmole) was added to a solution of 5-fluoro-3-piperidine-3-yl-1H-indole (220 mg, 1 mmole) in dioxane (8 ml). The reaction mixture was then boiled under reflux for 8 hours. The reaction mixture was worked up by distilling off the solvent. The residue contained, apart from nitrophenol, also the two diastereoisomers of 3-(5-fluoro-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 (30 g). Methanol/EE (1:1; 850 ml) was used as eluent. The non-polar diastereoisomer of 3-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (143 mg, m.p. 110°-115° C., 30%) and the polar diastereoisomer of 3-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (118 mg, m.p. 98°-101° C., 25%) were thereby obtained in pure form.

Workup

  1. temperatureunder reflux for 8 hours
  2. distillationby distilling off the solvent
  3. customThe diastereoisomers were separated
  4. custompurified by flash chromatography on silica gel (30 g)

Sources & evidence

ORD record
ord-f496548184954b91b9a5431a424825b6
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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