N,N'-Dicyclohexylurea → HCID 10345144, compound

HRID 2357505Notes

Reaction equation

HRID 2357505 reaction equation
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]([CH3:51])[C:34]1([C:44]2[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=2)[CH2:39][CH2:38][C:37](=[CH: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>[CH3:51][N:33]([CH3:32])[C:34]1([C:44]2[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=2)[CH2:39][CH2:38][C:37](=[CH: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

Participants

10

Reactant 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 184096763-(pyrrolidin-3-yl)-1H-indoleHCID 67386288[4-Dimethylamino-4-(4-fluorophenyl)-cyclohexylidene)-acetic acid

Product 1

HCID 10345144HCID 10345144, compoundYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-hydroxybenzotriazole (1.08 mg, 8 mmole), 3-pyrrolidine-3-yl-1H-indole (744 mg, 4 mmole) and N-methylmorpholine (0.888 ml, 8 mmole) were added in succession under argon to a solution of [4-dimethylamino-4-(4-fluorophenyl)-cyclohexylidene)-acetic acid (1.055 g, 4 mmole) in dry dimethylformamide (40 ml). The clear solution was cooled in an ice bath and dicyclohexylcarbodiimide (1.65 g, 8 mmole) was added. The reaction mixture was stirred for 5 days at room temperature, 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 filtrate was diluted with water (300 ml) and 5M sodium hydroxide (7 ml, 35 mmole) was added. The crude product of 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone thereupon precipitated out as a beige-coloured solid (1.67 g). The chromatographic separation on silica gel (80 g) was carried out with EE/methanol (1:1). 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone was thereby obtained as a diastereoisomer mixture in a yield of 52% (916 mg) in the form of a colourless solid with a melting point of 109°-112° C.

Workup

  1. temperatureThe clear 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. customThe crude product of 2-(4-dimethylamino-4-(4-fluorophenyl)cyclohexylidene)-1-[3-(1H-indol-3-yl)pyrrolidine-1-yl]-ethanone thereupon precipitated out as a beige-coloured solid (1.67 g)
  9. customThe chromatographic separation on silica gel (80 g)

Sources & evidence

ORD record
ord-2e52962d14994765a3a2d19e72997bbb
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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