Dichloromethane → (R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea	HCID 16125103	—
Reactant	(R)-Methyl 2-(5-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate	HCID 86673568	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	Dimethylformamide	HCID 6228	—
Product	(R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate	HCID 131731536	—

Reaction Conditions

Temperature	82.5 °C

Reaction Steps

The compound of example 359 (288 mg, 0.886 mmol), compound of example 357 (300 mg, 0.738 mmol) and Pd(dppf)Cl2: CH2Cl2 (18 mg, 0.022 mmol) were taken in DMF (5 mL) under an argon atmosphere. To this reaction mixture, 2M solution of Na2CO3 (234 mg, 2.214 mmol, 1.1 mL) was added and the reaction mixture was stirred at 80-85° C. for 1 to 1.5 h. After completion of the reaction, water was added to the reaction mixture and the product obtained was extracted with ether. The combined ether layers were washed with water and brine, dried over anhydrous Na2SO4 or MgSO4. The solvent was evaporated and the product was purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether) to obtain the title compound.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08748426B2
Source dataset	uspto-grants-2014_06
ORD ID	ord-6fe32822517e4cbaafc362f966cf49cd
Source note	uspto-grants-2014_06