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

HRID 1891270Notes

Reaction equation

HRID 1891270 reaction equation
Br[C:2]1[CH:18]=[CH:17][C:5]([CH2:6][N:7]2[CH2:11][C:10](=[O:12])[N:9]([CH:13]3[CH2:15][CH2:14]3)[C:8]2=[O:16])=[CH:4][CH:3]=1.[CH:19]1([N:22]2[CH2:30][C:29]3[C:24](=[CH:25][CH:26]=[C:27](B4OC(C)(C)C(C)(C)O4)[CH:28]=3)[C:23]2=[O:40])[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:13]1([N:9]2[C:10](=[O:12])[CH2:11][N:7]([CH2:6][C:5]3[CH:17]=[CH:18][C:2]([C:27]4[CH:28]=[C:29]5[C:24](=[CH:25][CH:26]=4)[C:23](=[O:40])[N:22]([CH:19]4[CH2:21][CH2:20]4)[CH2:30]5)=[CH:3][CH:4]=3)[C:8]2=[O:16])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 594023502-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 66813314HCID 66813314, compound

Product 1

HCID 529323943-Cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dioneYield 53.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(4-bromobenzyl)-3-cyclopropylimidazolidine-2,4-dione (7H5) (0.1 mmol, 30 mg), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.1 mmol, 31.0 mg), tris(dibenzylidineacetone)dipalladium (0.005 mmol, 4.59 mg), tricyclohexylphosphine (0.012 mmol, 3.37 mg) and potassium phosphate (0.17 mmol, 36.1 mg) were suspended in dioxane (1 ml) and water (0.5 ml) and heated to 130° C. in the microwave for 15 min. The reaction mixture was quenched with 2 ml of water and 3 ml of DCM and the organic phase separated using a hydrophobic fritted tube. The organic phase was concentrated and the residue purified by prep basic HPLC to give 3-cyclopropyl-1-(4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)imidazolidine-2,4-dione (Example 7a) 21.3 mg (53%); 1H NMR (400 MHz, CDCl3) δ 7.88 (d, 1H) 7.63 (d, 1H) 7.58 (m, 3H) 7.35 (d, 2H) 4.59 (s, 2H) 4.37 (s, 2H) 3.71 (s, 2H) 2.96 (m, 1H) 2.64 (m, 1H) 1.01-0.86 (m, 8H) LCMS m/z (M+H) 402.2.

Workup

  1. customThe reaction mixture was quenched with 2 ml of water and 3 ml of DCM
  2. customthe organic phase separated
  3. concentrationThe organic phase was concentrated
  4. customthe residue purified by prep basic HPLC

Sources & evidence

ORD record
ord-d1226a04fb9d4fe4a3c674fdb3500300
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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