N,N'-Dicyclohexylurea → HCID 9983901, compound

HRID 2357458Notes

Reaction equation

HRID 2357458 reaction equation
ON1C2C=CC=CC=2N=N1.[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][CH:16]=[C:15]2[CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.CN1CCOCC1.[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.C(NC1CCCCC1)(NC1CCCCC1)=O.[OH-].[Na+]>CN(C)C=O.C(Cl)Cl.O>[Cl:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][CH:16]=[C:15]2[CH:21]1[CH2:26][CH2:25][N:24]([C:43](=[O:44])[CH:42]=[C:39]2[CH2:38][CH2:37][C:36]([N:35]([CH3:52])[CH3:34])([C:46]3[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=3)[CH2:41][CH2:40]2)[CH2:23][CH2:22]1

Participants

11

Reactant 7

HCID 4277N,N'-DicyclohexylureaHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 128313754-(5-chloro-[1H]-indol-3-yl)-piperidineHCID 574382874-Dimethylamino-4-phenylcyclohexylidene-acetic acid

Product 1

HCID 9983901HCID 9983901, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-hydroxybenzotriazole (405 mg, 3.0 mmole), 5-chloro-3-piperidine-4-yl-1H indole (352 mg, 1.5 mmole) and N-methylmorpholine (0.333 ml, 3.0 mmole) were added in succession under argon to a solution of (4-dimethylamino-4-phenylcyclohexylidene)-acetic acid (444 mg, 1.5 mmole) in dry dimethylformamide (10 ml). The solution was cooled in an ice bath and dicyclohexylcarbodiimide (618 mg, 3.0 mmole) was added. The reaction mixture was stirred for 7 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). Oily products thereupon precipitated out, which could not be separated by filtration. The reaction mixture was extracted with DCM (3×50 ml), water (300 ml) and 5M sodium hydroxide (7 ml, 35 mmole) were added to the aqueous phase, and the whole was kept for 16 hours at 5° C. 1-[4-(5-chloro-1H-indol-3-yl)piperidine-1-yl]-2-(4-dimethylamino-4-phenylcyclo-hexylidene)-ethanone thereupon precipitated out as a yellow solid (167 mg, 23%) with an m.p. of 115°-119° C.

Workup

  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. customOily products thereupon precipitated out
  6. customwhich could not be separated by filtration
  7. additionwere added to the aqueous phase
  8. waitthe whole was kept for 16 hours at 5° C
  9. custom1-[4-(5-chloro-1H-indol-3-yl)piperidine-1-yl]-2-(4-dimethylamino-4-phenylcyclo-hexylidene)-ethanone thereupon precipitated out as a yellow solid (167 mg, 23%) with an m.p. of 115°-119° C.

Sources & evidence

ORD record
ord-7f778af93b9340ff92388f5b9f1abcec
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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