Potassium Phosphate, Tribasic → HCID 67173284, compound

HRID 1891271Notes

Reaction equation

HRID 1891271 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[C:11]([CH3:13])([CH3:12])[C:10](=[O:14])[NH:9][C:8]2=[O:15])=[CH:4][CH:3]=1.BrC1C=CC(CN2CC(=O)NC2=O)=CC=1.[CH:33]1([N:36]2[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[C:41](B4OC(C)(C)C(C)(C)O4)[CH:42]=3)[C:37]2=[O:54])[CH2:35][CH2:34]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:33]1([N:36]2[CH2:44][C:43]3[C:38](=[CH:39][CH:40]=[C:41]([C:2]4[CH:17]=[CH:16][C:5]([CH2:6][N:7]5[C:11]([CH3:13])([CH3:12])[C:10](=[O:14])[NH:9][C:8]5=[O:15])=[CH:4][CH:3]=4)[CH:42]=3)[C:37]2=[O:54])[CH2:35][CH2:34]1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 154067221-(4-Bromobenzyl)imidazolidine-2,4-dioneHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 64217701HCID 64217701, compound

Product 1

HCID 67173284HCID 67173284, compoundYield 54.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(4-bromobenzyl)-5,5-dimethylimidazolidine-2,4-dione (8B4) (0.168 mmol, 50 mg) (prepared according to the method described for intermediate (1B4), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.1 mmol, 53.0 mg), tris(dibenzylidineacetone)dipalladium (0.008 mmol, 8.1 mg), tricyclohexylphosphine (0.02 mmol, 5.7 mg) and potassium phosphate (0.27 mmol, 60.7 mg) were suspended in dioxane (3 ml) and water (1 ml) and heated to 130° C. in the microwave for 15 min. The reaction mixture was quenched with water (6 ml) and DCM (9 ml) and the organic layer separated using a hydrophobic fritted tube. The organic phase was concentrated and the residue purified on silica eluting with 0-100% EtOAc/heptane to give 1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-5,5-dimethylimidazolidine-2,4-dione (8I1) 21.3 mg (53%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.54 (d, 1H) 7.57 (m, 3H) 7.43 (d, 2H) 7.33 (bs, 1H) 4.56 (s, 2H) 4.37 (s, 2H) 3.94 (m, 1H) 1.34 (s, 6H) 0.95-0.88 (m, 4H).

Workup

  1. customThe reaction mixture was quenched with water (6 ml) and DCM (9 ml)
  2. customthe organic layer separated
  3. concentrationThe organic phase was concentrated
  4. customthe residue purified on silica eluting with 0-100% EtOAc/heptane

Sources & evidence

ORD record
ord-4e87aa69028842548b93bd19280714cc
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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