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

HRID 598461Notes

Reaction equation

HRID 598461 reaction equation
ClC1(N)C=CC([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])=CC1.[C:23]([O:34][CH3:35])(=[O:33])[C:24]1[CH:32]=[CH:31][CH:30]=[C:26]([C:27]([O-])=O)[CH:25]=1.[CH:36]1[CH:37]=C[C:39]2N(O)N=[N:42][C:40]=2[CH:41]=1.[OH2:46].CN1C[CH2:52][O:51]CC1.CCN=C=NCCCN(C)C.[ClH:65]>CN(C=O)C.CCOC(C)=O>[Cl:65][C:27]1([C:26]2[CH:30]=[CH:31][CH:32]=[C:24]([C:23]([O:34][CH3:35])=[O:33])[CH:25]=2)[CH:37]=[CH:36][C:41]([NH:10][C:9]([NH:8][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:19])([F:20])[F:21])=[O:11])=[C:40]([NH:42][C:52]([OH:51])=[O:46])[CH2:39]1

Participants

9

Reactant 6

HCID 962WaterHCID 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 866180784-chloro-3-((trifluoromethyl)phenyl)-N-(4-(3-methoxycarbonylphenyl)carboxyaminophenyl) ureaYield 43%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 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-bd2ea45aebbe4056ad24618ad6dfc0fd
Source dataset
uspto-grants-2011_03
Patent number
US07897623B2

Reaction notes

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