4-(5-chloro-[1H]-indol-3-yl)-piperidine → HCID 10327255, compound

HRID 2357449Notes

Reaction equation

HRID 2357449 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.[Cl: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]([Cl: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 128313754-(5-chloro-[1H]-indol-3-yl)-piperidineHCID 67531743(4-Dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester

Product 1

HCID 10327255HCID 10327255, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (774 mg, 2.2 mmole) was added to the suspension of 5-chloro-3-piperidine-4-yl-1H-indole (516 mg, 2.2 mmole) in dioxane (20 ml). The reaction mixture was a suspension also at 100° C., and was boiled under reflux for 40 hours. To work up the suspension the existing precipitate was filtered off, washed with dioxane (1×1 ml) and diethyl ether (3×2 ml) and dried in vacuo. The isolated solid (183 mg, 17%, m.p. 140°-150° C.) was a still unpurified part of the polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide, which was purified by flash chromatography on silica gel [20 g, eluent: methanol (500 ml)]. The mother liquor and the wash phases were concentrated by evaporation in vacuo. The residue contained in addition to phenol, also the two diastereoisomers of 4-(5-chloro-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 (75 g). Methanol/EE (1:1; 900 ml) was used as eluent. The non-polar diastereoisomer (335 mg, m.p. 205°-207° C., 31%) and the polar diastereoisomer of 4-(5-chloro-1H-indol-3-yl)piperidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (115 mg, m.p. 140°-143° C., 11%) were thereby obtained as pale yellow solids.

Workup

  1. customalso at 100° C.
  2. temperatureunder reflux for 40 hours
  3. filtrationwas filtered off
  4. washwashed with dioxane (1×1 ml) and diethyl ether (3×2 ml)
  5. customdried in vacuo
  6. customwas purified by flash chromatography on silica gel [20 g, eluent: methanol (500 ml)]
  7. concentrationThe mother liquor and the wash phases were concentrated by evaporation in vacuo
  8. additionThe residue contained in addition to phenol
  9. customThe diastereoisomers were separated
  10. custompurified by flash chromatography on silica gel (75 g)

Sources & evidence

ORD record
ord-f9a0608ba0714007a0897363324e071d
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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