4-Methylmorpholine → 2-(4-Dimethylamino-4-phenylcyclohexylidene)-N-[5-(1H-indol-3-yl)pentyl]acetamide

HRID 908941Notes

Reaction equation

HRID 908941 reaction equation
ON1C2C=CC=CC=2N=N1.[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])=[CH:12]1.CN1CCOCC1.Cl.[CH3:34][N:35]([CH3:52])[C:36]1([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:41][CH2:40][C:39](=[CH:42][C:43](O)=[O:44])[CH2:38][CH2:37]1.C1(N=C=NC2CCCCC2)CCCCC1.[OH-].[Na+]>CN(C)C=O.O>[CH3:52][N:35]([CH3:34])[C:36]1([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)[CH2:41][CH2:40][C:39](=[CH:42][C:43]([NH:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[NH:11][CH:12]=2)=[O:44])[CH2:38][CH2:37]1

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 358725-(1H-indol-3-yl)pentan-1-amineHCID 757711-HydroxybenzotriazoleHCID 67386703(4-Dimethylamino-4-phenylcyclohexylidene)acetic acid hydrochloride

Product 1

HCID 116914922-(4-Dimethylamino-4-phenylcyclohexylidene)-N-[5-(1H-indol-3-yl)pentyl]acetamideYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-Hydroxybenzotriazole (819 mg, 6.0 mmol), 5-(1H-indol-3-yl)pentylamine (606 mg, 3.0 mmol) and N-methylmorpholine (0.666 ml, 6.0 mmol) were added to a solution of (4-dimethylamino-4-phenylcyclohexylidene)acetic acid hydrochloride (887 mg, 3.0 mmol) in dry dimethylformamide (10 ml) under argon. The solution was cooled to 0° C. and dicyclohexylcarbodiimide (1.25 g, 6.0 mmol) was added. The reaction mixture was stirred at RT for 4 d. Working up of the mixture was carried out by separating off the urea which had precipitated out and introducing the filtrate into a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Still further urea thereby precipitated out and was separated off. The aqueous phase was diluted with water (300 ml), 5 M sodium hydroxide solution (7 ml, 35 mmol) was added and the mixture was stored at 5° C. for 3 d. The crude product thereby precipitated out as a beige-coloured solid in a yield of 69% (915 mg). After chromatography on silica gel (50 mg) with EA/methanol (1:1) and methanol, the product was isolated as a colourless solid (333 mg) with an m.p. of 68-72° C. in a yield of 25%.

Workup

  1. customby separating off the urea which
  2. customhad precipitated out
  3. additionintroducing the filtrate
  4. additioninto a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml)
  5. customStill further urea thereby precipitated out and
  6. customwas separated off
  7. additionwas added
  8. waitthe mixture was stored at 5° C. for 3 d
  9. customThe crude product thereby precipitated out as a beige-coloured solid in a yield of 69% (915 mg)

Sources & evidence

ORD record
ord-e5a05ad6568443509f49f91c8c896946
Source dataset
uspto-grants-2011_09
Patent number
US08017630B2

Reaction notes

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