Potassium Phosphate, Tribasic → HCID 52931853, compound

HRID 1891259Notes

Reaction equation

HRID 1891259 reaction equation
Br[C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[CH2:11][C:10](=[O:12])[N:9]([CH2:13][CH3:14])[C:8]2=[O:15])=[C:4]([Cl:18])[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>[Cl:18][C:4]1[CH:3]=[C:2]([C:27]2[CH:28]=[C:29]3[C:24](=[CH:25][CH:26]=2)[C:23](=[O:40])[N:22]([CH:19]2[CH2:21][CH2:20]2)[CH2:30]3)[CH:17]=[CH:16][C:5]=1[CH2:6][N:7]1[CH2:11][C:10](=[O:12])[N:9]([CH2:13][CH3:14])[C:8]1=[O:15]

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 67172547HCID 67172547, compound

Product 1

HCID 52931853HCID 52931853, compoundYield 33.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(4-Bromo-2-chlorobenzyl)-3-ethylimidazolidine-2,4-dione (2C5) (0.106 mmol, 35 mg), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (106 mmol, 31.6 mg), tris(dibenzylidineacetone)dipalladium (0.005 mmol, 4.8 mg), tricyclohexylphosphine (0.013 mmol, 3.6 mg) and potassium phosphate (0.317 mmol, 67 mg) were dissolved in dioxane (2 ml) and water (1 ml) and the mixture was heated at 120° C. in the microwave for 30 min. The sample was concentrated and partitioned between DCM and water and the organic layer collected and dried using a hydrophobic fritted tube before concentration. Purification using basic semi-prep HPLC afforded 1-(2-chloro-4-(2-cyclopropyl-1-oxoisoindolin-5-yl)benzyl)-3-ethylimidazolidine-2,4-dione (Example 2a) 15.1 mg (33%); 1H NMR (400 MHz, CDCl3) δ 7.90 (d, 1H) 7.62 (m, 2H) 7.56 (s, 1H) 7.51 (d, 1H) 7.43 (d, 1H) 4.76 (s, 2H) 4.39 (s, 2H) 3.85 (s, 2H) 3.61 (q, 2H) 2.98 (m, 1H) 1.25 (t, 3H) 0.96-89 (m, 4H); LCMS m/z (M+H) 424.0.

Workup

  1. concentrationThe sample was concentrated
  2. custompartitioned between DCM and water
  3. customthe organic layer collected
  4. customdried
  5. concentrationbefore concentration
  6. customPurification

Sources & evidence

ORD record
ord-334b4c380eec4da599c94111862e984a
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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