Dichloromethane → (R)-Methyl-3-methyl-2-(1-oxo-6-(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-(6-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate	HCID 131731530	—
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-6-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate	HCID 67306227	—

Reaction Conditions

Temperature	82.5 °C

Reaction Steps

The compound of example 329 (288 mg, 0.886 mmol), compound of example 327 (300 mg, 0.738 mmole) 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 mmole, 1.1 mL) was added. The reaction mixture was stirred at 80-85° C. for 1 to 1.5 h. After completion of the reaction, water was added and the product obtained was extracted with ether. The ether layer was washed with water, brine and dried over anhydrous Na2SO4 or anhydrous MgSO4. The solvent was evaporated and the residue obtained was purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether) 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-22a0b2456b974c319a90cda0cbf3556d
Source note	uspto-grants-2014_06