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

HRID 2357461Notes

Reaction equation

HRID 2357461 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.[NH:26]1[CH2:31][CH2:30][CH:29]([C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[NH:34][CH:33]=2)[CH2:28][CH2:27]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:26]2[CH2:31][CH2:30][CH:29]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[NH:34][CH:33]=3)[CH2:28][CH2:27]2)=[O:25])[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 7022353-(4-Piperidinyl)-1H-indoleHCID 67531726(4-Dimethylamino-4-phenylcyclohexyl)-carbamic acid phenyl ester

Product 1

HCID 99826474-(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 (316 mg, 0.93 mmole) was added to a solution of 3-piperidine-4-yl-1H-indole (187 mg, 0.93 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 4-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was recrystallised from methanol (5 ml). It was obtained as a colourless solid in a yield of 210 mg (51%).

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 4-(1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl)-amide was recrystallised from methanol (5 ml)
  8. customIt was obtained as a colourless solid in a yield of 210 mg (51%)

Sources & evidence

ORD record
ord-4aabc3ed9a324540ae1704fcede2e240
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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