4-Methylmorpholine → 4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl)carbamoylphenyl)urea

HRID 2078578Notes

Reaction equation

HRID 2078578 reaction equation
[Cl:1][C:2]1(C2C=CC=C(C(=O)NC)C=2)[CH:7]=[CH:6][C:5]([N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])[C:9](=[O:11])[NH2:10])=[C:4](NC(O)=O)[CH2:3]1.[CH3:36][NH:37][C:38]([C:40]1[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=1)[NH2:43])=[O:39].C1C=CC2N(O)N=NC=2C=1.O.CN1CC[O:62][CH2:61]C1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[Cl:1][C:2]1([C:61](=[O:62])[NH:43][C:42]2[CH:44]=[CH:45][CH:46]=[C:40]([C:38](=[O:39])[NH:37][CH3:36])[CH:41]=2)[CH:7]=[CH:6][C:5]([N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:19])([F:21])[F:20])[C:9](=[O:11])[NH2:10])=[CH:4][CH2:3]1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 6765263-Amino-N-methylbenzamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 865836114-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl) carboxyaminophenyl)urea

Product 1

HCID 865836104-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl)carbamoylphenyl)ureaYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-chloro-3-((trifluoromethyl)phenyl)-N′-(4-(3-methylcarbamoylphenyl)carboxyaminophenyl) urea (0.14 g, 0.48 mmol), 3-methylcarbamoylaniline (0.080 g, 0.53 mmol), HOBT-H2O (0.14 g, 1.07 mmol), and N-methylmorpholine (0.5 mL, 1.07 mmol) in DMF (3 mL) at 0° C. was added EDCI.HCl (0.10 g, 0.53 mmol). The resulting mixture was allowed to warm to room temp. and was stirred overnight. The resulting mixture was treated with water (10 mL), and extracted with EtOAc (25 mL). The organic phase was concentrated under reduced pressure. The resulting yellow solids were dissolved in EtOAc (3 mL) then filtered through a pad of silica gel (17 g, gradient from 70% EtOAc/30% hexane to 10% MeOH/90% EtOAc) to give N-(4-chloro-3-((trifluoromethyl)phenyl)-N′-(4-(3-methylcarbamoylphenyl)carbamoylphenyl) urea as a white solid (0.097 g, 41%): mp 225-229; TLC (100% EtOAc) Rf 0.23.

Workup

  1. temperatureto warm to room temp.
  2. extractionextracted with EtOAc (25 mL)
  3. concentrationThe organic phase was concentrated under reduced pressure
  4. dissolutionThe resulting yellow solids were dissolved in EtOAc (3 mL)
  5. filtrationthen filtered through a pad of silica gel (17 g, gradient from 70% EtOAc/30% hexane to 10% MeOH/90% EtOAc)

Sources & evidence

ORD record
ord-e0a96bcba55545f1a191dac971b476df
Source dataset
uspto-grants-2011_04
Patent number
US07928239B2

Reaction notes

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