Potassium Phosphate, Tribasic → HCID 67172819, compound

HRID 1891277Notes

Reaction equation

HRID 1891277 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[C:22](=[O:26])[N:21]([CH:27]1[CH2:29][CH2:28]1)[CH2:20]2)[CH2:5][N:6]1[CH2:10][C:9](=[O:11])[N:8]([CH3:12])[C:7]1=[O:13].[CH3:30]B1OB(C)OB(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH:27]1([N:21]2[CH2:20][C:19]3[C:23](=[CH:24][CH:25]=[C:17]([C:16]4[CH:15]=[CH:14][C:4]([CH2:5][N:6]5[CH2:10][C:9](=[O:11])[N:8]([CH3:12])[C:7]5=[O:13])=[CH:3][C:2]=4[CH3:30])[CH:18]=3)[C:22]2=[O:26])[CH2:28][CH2:29]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 574072TrimethylboroxineHCID 52931965HCID 52931965, compound

Product 1

HCID 67172819HCID 67172819, compoundYield 39.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(3-chloro-4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-methylimidazolidine-2,4-dione (0.073 mmol, 30 mg), trimethylboroxine (0.110 mmol, 27.6 mg), tris(dibenzylideneacetone)dipalladium(0) (3.66 μmol, 3.4 mg), tricyclohexylphosphine (8.78 μmol, 2.5 mg) and potassium phosphate, tribasic (0.124 mmol, 26.4 mg) were suspended in dioxane (750 μL) and water (250 μL) and heated under microwave irradiation at 130° C. for 30 minutes. The solvent was removed under reduced pressure and the mixture partitioned between water and dichloromethane. The organic layer was separated using a hydrophobic frit and concentrated. Purified by acidic prep HPLC to afford 1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)-3-methylbenzyl)-3-methylimidazolidine-2,4-dione (11.2 mg, 39%); 1H NMR (400 MHz, CDCl3) 7.86 (d, 1H), 7.36 (dd, 1H), 7.31 (d, 1H), 7.21-7.12 (m, 3H), 4.58 (s, 2H), 4.36 (s, 2H), 3.79 (s, 2H), 3.07 (s, 3H), 2.96 (m, 1H), 2.24 (s, 3H), 0.97-0.87 (m, 4H). LCMS (M+H) 390.2.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe mixture partitioned between water and dichloromethane
  3. customThe organic layer was separated
  4. concentrationconcentrated
  5. customPurified by acidic prep HPLC

Sources & evidence

ORD record
ord-a52a23787b77497392a616021ddcb0c9
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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