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

HRID 2357477Notes

Reaction equation

HRID 2357477 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.[F:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[CH:36]1[CH2:41][CH2:40][CH2:39][NH:38][CH2:37]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:38]2[CH2:39][CH2:40][CH2:41][CH:36]([C:30]3[C:29]4[C:33](=[CH:34][CH:35]=[C:27]([F:26])[CH:28]=4)[NH:32][CH:31]=3)[CH2:37]2)=[O:25])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 574383045-fluoro-3-(piperidin-3-yl)-1H-indoleHCID 67531726(4-Dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester

Product 1

HCID 593855673-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The polar diastereoisomer of (4-dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester (338 mg, 1 mmole) was added to a solution of 5-fluoro-3-piperidine-3-yl-1H-indole (218 mg, 1 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 (3×15 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The polar diastereoisomer of 3-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was purified by column chromatography [silica gel 60 (25 g); methanol (250 ml)]. It was obtained as a colourless solid in a yield of 200 mg (43%).

Workup

  1. temperatureunder reflux for 32 hours
  2. distillationby distilling off dioxane
  3. additiondiluting with water (10 ml)
  4. extractionextracted with EE (3×15 ml)
  5. dry with materialThe organic phase was dried with Na2SO4
  6. concentrationconcentrated by evaporation
  7. customThe polar diastereoisomer of 3-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was purified by column chromatography [silica gel 60 (25 g); methanol (250 ml)]
  8. customIt was obtained as a colourless solid in a yield of 200 mg (43%)

Sources & evidence

ORD record
ord-f5bc3a182c614be9afca10d1b8a93216
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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