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

Participants

Role	Name	HCID	Charge
Reactant	Dimethylformamide	HCID 6228	—
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	1-Hydroxybenzotriazole hydrate	HCID 2796029	—
Reactant	1,3-Benzenedicarboxylic acid, monomethyl ester	HCID 6951279	—
Reactant	4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-aminophenyl)urea	HCID 86583609	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-carbomethoxyphenyl)carboxyaminophenyl)urea	HCID 86583608	43%

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US07351834B1
Source dataset	uspto-grants-2008_04
ORD ID	ord-d786a575a12047f68a81115bfcc57d9b
Source note	uspto-grants-2008_04