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

HRID 403955

Reaction equation

HRID 403955 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C@H:12]([CH:17]([CH3:19])[CH3:18])[C:13]([O:15][CH3:16])=[O:14])[CH2:5]2.CC1(C)C(C)(C)OB([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=3)=[O:36])=[CH:30][CH:29]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:18][CH:17]([CH3:19])[C@@H:12]([N:6]1[CH2:5][C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:28]3[CH:29]=[CH:30][C:31]([NH:34][C:35]([NH:37][C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([C:44]([F:45])([F:46])[F:47])[CH:39]=4)=[O:36])=[CH:32][CH:33]=3)[CH:3]=2)[C:7]1=[O:11])[C:13]([O:15][CH3:16])=[O:14]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 161251031-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)ureaHCID 86673568(R)-Methyl 2-(5-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate

Product 1

HCID 131731536(R)-Methyl 3-methyl-2-(1-oxo-5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
82.5 °C

Procedure

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.

Workup

  1. additionwas added to the reaction mixture
  2. customthe product obtained
  3. extractionwas extracted with ether
  4. washThe combined ether layers were washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4 or MgSO4
  6. customThe solvent was evaporated
  7. customthe product was purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-6fe32822517e4cbaafc362f966cf49cd
Source dataset
uspto-grants-2014_06
Patent number
US08748426B2

Linked notes

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