5-fluoro-3-(piperidin-4-yl)-1H-indole → HCID 11765016, compound

HRID 2357454Notes

Reaction equation

HRID 2357454 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.[F: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: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:40]2[CH2:41][CH2:42][CH:37]([C:31]3[C:30]4[C:34](=[CH:35][CH:36]=[C:28]([F:27])[CH:29]=4)[NH:33][CH:32]=3)[CH2:38][CH2:39]2)=[O:7])[CH2:12][CH2:13]1

Participants

4

Reactant 2

HCID 117699295-fluoro-3-(piperidin-4-yl)-1H-indoleHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 11765016HCID 11765016, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (387.7 mg, 1.1 mmole) was added to a solution of 5-fluoro-3-piperidine-4-yl-1H-indole (240.1 mg, 1.1 mmole) in dioxane (11 ml). The solution was boiled under reflux for 16 hours. The solution was worked up by distilling off the solvent in vacuo. The residue contained, apart from phenol, also the two diastereoisomers of 4-(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 (25 g). Methanol/EE (1:1, 900 ml) was used as eluent. The non-polar diastereoisomer (150 mg, m.p. 95°-98° C., 29%) and the polar diastereoisomer of 4-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (120 mg, m.p. 206°-208° C., 23%) were thereby obtained in pure form.

Workup

  1. temperatureunder reflux for 16 hours
  2. distillationby distilling off the solvent in vacuo
  3. customThe diastereoisomers were separated
  4. custompurified by flash chromatography on silica gel (25 g)

Sources & evidence

ORD record
ord-ff11254275394e418028844749e66ad3
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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