Water → 4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-carbomethoxyphenyl)carboxyaminophenyl)urea

HRID 78334Notes

Reaction equation

HRID 78334 reaction equation
[Cl:1][C:2]1(N)[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])=[CH:4][CH2:3]1.[C:23]([O:34][CH3:35])(=[O:33])[C:24]1[CH:32]=[CH:31][CH:30]=[C:26](C([O-])=O)[CH:25]=1.C1C=CC2N([OH:45])N=NC=2C=1.O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.C[N:67]([CH:69]=[O:70])C>CCOC(C)=O>[Cl:1][C:2]1([C:31]2[CH:30]=[CH:26][CH:25]=[C:24]([C:23]([O:34][CH3:35])=[O:33])[CH:32]=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]([NH:67][C:69]([OH:70])=[O:45])[CH2:3]1

Participants

9

Reactant 7

HCID 962WaterHCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69512791,3-Benzenedicarboxylic acid, monomethyl esterHCID 865836094-chloro-3-((trifluoromethyl)phenyl)-N'-(4-aminophenyl)urea

Product 1

HCID 865836084-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-carbomethoxyphenyl)carboxyaminophenyl)ureaYield 43%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(4-chloro-3-((trifluoromethyl)phenyl)-N′-(4-aminophenyl)urea (Method C1d; 0.050 g, 1.52 mmol), mono-methyl isophthalate (0.25 g, 1.38 mmol), HOBT.H2O (0.41 g, 3.03 mmol) and N-methylmorpholine (0.33 mL, 3.03 mmol) in DMF (8 mL) was added EDCI.HCl (0.29 g, 1.52 mmol). The resulting mixture was stirred at room temp. overnight, diluted with EtOAc (25 mL) and sequentially washed with water (25 mL) and a saturated NaHCO3 solution (25 mL). The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The resulting solids were triturated with an EtOAc solution (80% EtOAc/20% hexane) to give N-(4-chloro-3-((trifluoromethyl)phenyl)-N′-(4-(3-methoxycarbonylphenyl)carboxyaminophenyl)urea (0.27 g, 43%): mp 121-122; TLC (80% EtOAc/20% hexane) Rf 0.75.

Workup

  1. washsequentially washed with water (25 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting solids were triturated with an EtOAc solution (80% EtOAc/20% hexane)

Sources & evidence

ORD record
ord-e5aa6c48bc814df79ad2320b5daa0559
Source dataset
uspto-grants-2014_09
Patent number
US08841330B2

Reaction notes

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