Potassium Phosphate, Tribasic → HCID 52932398, compound

HRID 1891276Notes

Reaction equation

HRID 1891276 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10]2=[O:16])=[N:6][CH:7]=1.[CH:17]1([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25](B4OC(C)(C)C(C)(C)O4)[CH:26]=3)[C:21]2=[O:38])[CH2:19][CH2:18]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[CH:17]1([N:20]2[CH2:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([C:2]4[CH:3]=[CH:4][C:5]([CH2:8][N:9]5[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10]5=[O:16])=[N:6][CH:7]=4)[CH:26]=3)[C:21]2=[O:38])[CH2:19][CH2:18]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 67172220HCID 67172220, compound

Product 1

HCID 52932398HCID 52932398, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1-((5-Bromopyridin-2-yl)methyl)-3-methylimidazolidine-2,4-dione (9J5) (0.229 mmol, 65 mg), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-one (1A5) (0.229 mmol, 68.0 mg), tris(dibenzylidineacetone)dipalladium (0.011 mmol, 10.5 mg), tricyclohexylphosphine (0.027 mMol, 7.7 mg) and potassium phosphate (0.389 mmol, 83.0 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 then passed through a hydrophobic fritted tube, washing with DCM. The organic layers were concentrated and the residue purified by basic prep HPLC to give 1-((5-(2-cyclopropyl-1-oxoisoindolin-5-yl)pyridin-2-yl)methyl)-3-methylimidazolidine-2,4-dione (Example 9a) 27.6 mg (32.1%); 1H NMR (400 MHz, CDCl3) 8.79 (dd, 1H) 7.91 (m, 2H) 7.64 (dd, 1H) 7.59 (s, 1H) 7.39 (d, 1H) 4.75 (s, 2H) 4.40 (s, 2H) 4.04 (s, 2H) 3.07 (s, 3H) 2.97 (m, 1H) 0.97-0.88 (m, 4H) LCMS m/z (M+H) 377.2.

Workup

  1. customThe reaction mixture was quenched with 2 ml of water and 3 ml of DCM
  2. custompassed through a hydrophobic fritted tube
  3. washwashing with DCM
  4. concentrationThe organic layers were concentrated
  5. customthe residue purified by basic prep HPLC

Sources & evidence

ORD record
ord-e1f494ac23fc48648a21bee5e852cade
Source dataset
uspto-grants-2013_08
Patent number
US08507521B2

Reaction notes

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