N,N'-Dicyclohexylurea → 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)piperidine-1-yl]-ethanone

HRID 2357491Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2357491
ON1C2C=CC=CC=2N=N1.[NH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=2)[CH2:12]1.CN1CCOCC1.[CH3:33][N:34]([CH3:51])[C:35]1([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:40][CH2:39][C:38](=[CH:41][C:42](O)=[O:43])[CH2:37][CH2:36]1.C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O.[OH-].[Na+]>CN(C)C=O.O>[CH3:51][N:34]([CH3:33])[C:35]1([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:40][CH2:39][C:38](=[CH:41][C:42]([N:11]2[CH2:16][CH2:15][CH2:14][CH:13]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[NH:19][CH:18]=3)[CH2:12]2)=[O:43])[CH2:37][CH2:36]1

Komponenten

10

Edukt 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 153894433-(Piperidin-3-YL)-1H-indoleHCID 574382874-Dimethylamino-4-phenylcyclohexylidene-acetic acid

Produkt 1

HCID 99567182-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)piperidine-1-yl]-ethanoneAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-hydroxybenzotriazole (675 mg, 5.0 mmole), 3-piperidine-3-yl-1H-indole (500 mg, 2.5 mmole) and N-methylmorpholine (0.555 ml, 5.0 mmole) were added in succession under argon to a solution of (4-dimethylamino-4-phenylcyclohexylidene)-acetic acid (739 mg, 2.5 mmole) in dry dimethylformamide (10 ml). The solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.03 g, 5.0 mmole) was added. The reaction mixture was stirred for 5 days at RT, the dicyclohexylurea precipitating out little by little. The reaction mixture was worked up by separating the precipitated urea and adding the filtrate to a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Further urea together with 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)-piperidine-1-yl]-ethanone thereupon precipitated out (1.5 g). The aqueous phase was diluted with water (300 ml), 5M sodium hydroxide (7 ml, 35 mmole) was added, and the whole was kept for 16 hours at 5° C. The crude product thereupon precipitated out as a colourless solid (464 mg). The crude product of 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)-piperidine-1-yl]-ethanone was purified chromatographically on silica gel (60 g) with EE/methanol (4:1) and (2:1) and obtained in a yield of 30% (322 mg)—2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)-piperidine-1-yl]-ethanone was obtained as a diastereoisomer mixture. A separation was not possible.

Aufarbeitung

  1. temperatureThe solution was cooled in an ice bath
  2. customby separating the precipitated urea
  3. additionadding the filtrate
  4. additionto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customFurther urea together with 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)-piperidine-1-yl]-ethanone thereupon precipitated out (1.5 g)
  6. additionwas added
  7. waitthe whole was kept for 16 hours at 5° C
  8. customThe crude product thereupon precipitated out as a colourless solid (464 mg)
  9. customThe crude product of 2-(4-dimethylamino-4-phenylcyclohexylidene)-1-[3-(1H-indol-3-yl)-piperidine-1-yl]-ethanone was purified chromatographically on silica gel (60 g) with EE/methanol (4:1) and (2:1)

Quellen und Nachweise

ORD-Eintrag
ord-b5b7c10c44e04ab9b41d9f2bbb0ccff9
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759385B2

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