Reaction #165516

Reaction equation

H2O

N-methylmorpholine

EDCI.HCl

DMF

4-chloro-3-((trifluoromethyl)phenyl)-N′-(4-aminophenyl)urea

mono-methyl isophthalate

HOBT

→

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

Yield 43.0%

Solvents

EtOAc

Conditions

Workup

1. 1
   Washsequentially washed with water (25 mL)
2. 2
   DryingThe organic layer was dried (Na2SO4)
3. 3
   Concentrationconcentrated under reduced pressure
4. 4
   OtherThe resulting solids were triturated with an EtOAc solution (80% EtOAc/20% hexane)

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.

Source