Potassium Phosphate, Tribasic → 3-(4-(2-Cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-1-methylimidazoline-2,4-dione

HRID 1891261Notes

Reaction equation

HRID 1891261 reaction equation
[CH:1]1([N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[C:9](B4OC(C)(C)C(C)(C)O4)[CH:10]=3)[C:5]2=[O:22])[CH2:3][CH2:2]1.Br[C:24]1[CH:38]=[CH:37][C:27]([CH2:28][N:29]2[C:33](=[O:34])[CH2:32][N:31]([CH3:35])[C:30]2=[O:36])=[CH:26][CH:25]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(Cl)Cl.O>[CH:1]1([N:4]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:24]4[CH:38]=[CH:37][C:27]([CH2:28][N:29]5[C:33](=[O:34])[CH2:32][N:31]([CH3:35])[C:30]5=[O:36])=[CH:26][CH:25]=4)[CH:10]=3)[C:5]2=[O:22])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 606247733-[(4-Bromophenyl)methyl]-1-methylimidazolidine-2,4-dione

Product 1

HCID 529318563-(4-(2-Cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-1-methylimidazoline-2,4-dioneYield 2,280.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.08 mmol, 26.4 mg), 3-(4-bromobenzyl)-1-methylimidazolidine-2,4-dione (3D3) (0.08 mmol, 25.0 mg), tris(dibenzylidineacetone)dipalladium (0.004 mmol, 4.12 mg), tricyclohexylphosphine (0.096 mmol, 3.1 mg) and potassium phosphate (0.16 mmol, 39.0 mg) were suspended in dioxane (1 ml) and water (0.5 ml) and heated at 120° C. in the microwave for 20 min. The reaction was diluted with DCM (2 ml) and water (2 ml) then passed through a hydrophobic fritted tube. The organic phase was concentrated and the residue purified on basic HPLC to give 3-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-1-methylimidazoline-2,4-dione (Example 3a) (685 mg, 55%) 1H NMR (400 MHz, CDCl3) δ 7.87 (d, 1H) 7.64 (d, 1H) 7.57-7.50 (m, 5H) 4.71 (s, 2H) 4.37 (s, 2H) 3.89 (s, 2H) 3.01 (s, 3H) 2.95 (m, 1H) 0.95-0.88 (m, 4H) LCMS m/z (M+H) 376.0.

Workup

  1. customthen passed through a hydrophobic fritted tube
  2. concentrationThe organic phase was concentrated
  3. customthe residue purified on basic HPLC

Sources & evidence

ORD record
ord-c494d3ee8ff4460992b26095e9dfa701
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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