3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole → 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide

HRID 2357452Notes

Reaction equation

HRID 2357452 reaction equation
[N+](C1C=CC([O:10][C:11](=O)[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.[NH:30]1[CH2:35][CH:34]=[C:33]([C:36]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[NH:38][CH:37]=2)[CH2:32][CH2:31]1>O1CCOCC1>[CH3:27][N:26]([CH3:28])[C:17]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:16][CH2:15][CH:14]([CH2:13][NH:12][C:11]([N:30]2[CH2:31][CH:32]=[C:33]([C:36]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[NH:38][CH:37]=3)[CH2:34][CH2:35]2)=[O:10])[CH2:19][CH2:18]1

Participants

4

Reactant 2

HCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 67532180(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid 4-nitrophenyl ester

Product 1

HCID 593855634-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amideYield 28.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid-4-nitro-phenyl ester (825.5 mg, 2.08 mmole) was added to a solution of 3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (411.8 mg, 2.08 mmole) in dioxane (10 ml). The reaction mixture formed a clear, reddish-brown solution above 60° C. The solution was boiled under reflux for 12 hours. The solution was worked up by distilling off the solvent in vacuo. The residue contained, apart from nitrophenol, also the two diastereoisomers of 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (120 g). Methanol (2000 ml) was used as eluent. The non-polar diastereoisomer (351 mg, m.p. 204°-206° C., 37%) and the polar diastereoisomer of 4-(1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (270 mg, m.p. 112°-115° C., 28%) were thereby obtained as pale yellow solids.

Workup

  1. customThe reaction mixture formed a clear, reddish-brown solution above 60° C
  2. temperatureunder reflux for 12 hours
  3. distillationby distilling off the solvent in vacuo
  4. customThe diastereoisomers were separated
  5. custompurified by flash chromatography on silica gel (120 g)

Sources & evidence

ORD record
ord-589b49bc473d477182153c3488e41772
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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