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

HRID 2357472Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2357472
ON1C2C=CC=CC=2N=N1.[NH:11]1[CH2:15][CH2:14][CH:13]([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)[CH2:12]1.CN1CCOCC1.[CH3:32][N:33]([CH3:50])[C:34]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH2:39][CH2:38][CH:37]([CH2:40][C:41](O)=[O:42])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O.[OH-].[Na+]>CN(C)C=O.O>[CH3:50][N:33]([CH3:32])[C:34]1([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:39][CH2:38][CH:37]([CH2:40][C:41]([N:11]2[CH2:15][CH2:14][CH:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH2:12]2)=[O:42])[CH2:36][CH2:35]1

Komponenten

10

Edukt 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 184096763-(pyrrolidin-3-yl)-1H-indoleHCID 67386132(4-Dimethylamino-4-phenylcyclohexyl)-acetic acid

Produkt 1

HCID 100047112-(4-dimethylamino-4-phenylcyclohexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanoneAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

1-hydroxybenzotriazole (810 mg, 6.0 mmole), 3-pyrrolidine-3-yl-1H-indole (558 mg, 3.0 mmole) and N-methylmorpholine (0.666 ml, 6.0 mmole) were added in succession under argon to a solution of (4-dimethylamino-4-phenylcyclohexyl)-acetic acid (897 mg, 3.0 mmole) in dry dimethylformamide (15 ml). The solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.2 g, 6.0 mmole) was added. The reaction mixture was stirred for 4 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 thereupon precipitated out, which was separated. The aqueous phase was diluted with water (300 ml), 5M sodium hydroxide (7 ml, 35 mmole) was added, and the reaction mixture was kept for 3 days at 5° C. The crude product of 2-(4-dimethylamino-4-phenylcyclo-hexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone precipitated out as a beige-coloured solid (1.11 g). After chromatographic separation on silica gel (80 g) with methanol 2-(4-dimethylamino-4-phenylcyclohexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone was isolated in a yield of 40% (521 mg) as a colourless solid with an m.p. of 98°-100° C.

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 thereupon precipitated out
  6. customwhich was separated
  7. additionwas added
  8. waitthe reaction mixture was kept for 3 days at 5° C
  9. customThe crude product of 2-(4-dimethylamino-4-phenylcyclo-hexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone precipitated out as a beige-coloured solid (1.11 g)
  10. customAfter chromatographic separation on silica gel (80 g) with methanol 2-(4-dimethylamino-4-phenylcyclohexyl)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone
  11. customwas isolated in a yield of 40% (521 mg) as a colourless solid with an m.p. of 98°-100° C.

Quellen und Nachweise

ORD-Eintrag
ord-ca0667a572d14e938c0faa9bfd66fdf8
Quelldatensatz
uspto-grants-2010_07
Patentnummer
US07759385B2

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