Dichloromethane → (R)-Methyl-3-methyl-2-(1-oxo-6-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoindolin-2-yl)butanoate

HRID 403931Notes

Reaction equation

HRID 403931 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([C@H:12]([CH:17]([CH3:19])[CH3:18])[C:13]([O:15][CH3:16])=[O:14])[C:8]2=[O:11])=[CH:4][CH:3]=1.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>[CH3:16][O:15][C:13](=[O:14])[C@H:12]([N:7]1[CH2:6][C:5]2[C: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][CH:4]=2)[C:8]1=[O:11])[CH:17]([CH3:19])[CH3:18]

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 131731530(R)-Methyl 2-(6-bromo-1-oxoisoindolin-2-yl)-3-methylbutanoate

Product 1

HCID 67306227(R)-Methyl-3-methyl-2-(1-oxo-6-(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 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.

Workup

  1. additionwas added
  2. customthe product obtained
  3. extractionwas extracted with ether
  4. washThe ether layer was washed with water, brine
  5. dry with materialdried over anhydrous Na2SO4 or anhydrous MgSO4
  6. customThe solvent was evaporated
  7. customthe residue obtained
  8. customwas purified by column chromatography (silica gel, 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-22a0b2456b974c319a90cda0cbf3556d
Source dataset
uspto-grants-2014_06
Patent number
US08748426B2

Reaction notes

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