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

関与物質

役割	名称	HCID	仕込み量
反応物	Dichloromethane	HCID 6344	—
反応物	Sodium Carbonate	HCID 10340	—
反応物	1-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea	HCID 16125103	—
反応物	(R)-Methyl 2-(5-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate	HCID 86673568	—
触媒	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
溶媒	Water	HCID 962	—
溶媒	Dimethylformamide	HCID 6228	—
生成物	(R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate	HCID 131731536	—

反応条件

温度	82.5 °C

反応手順

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.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08748426B2
出典データセット	uspto-grants-2014_06
ORD ID	ord-6fe32822517e4cbaafc362f966cf49cd
出典メモ	uspto-grants-2014_06