Sodium Carbonate → 5-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one

HRID 513248Notes

Reaction equation

HRID 513248 reaction equation
[OH:1][C:2]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[C:5](=[CH:6][CH:7]=[C:8](I)[CH:9]=2)[NH:4][C:3]1=[O:12].[CH3:19][C:20]1[C:24](B(O)O)=[C:23]([CH3:28])[O:22][N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1.O>[CH3:19][C:20]1[C:24]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][C:3](=[O:12])[C:2]3([OH:1])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:23]([CH3:28])[O:22][N:21]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 1175996703-Hydroxy-5-iodo-3-phenyl-1,3-dihydro-indol-2-one

Product 1

HCID 862961015-(3,5-Dimethylisoxazol-4-yl)-3-hydroxy-3-phenylindolin-2-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
130 °C

Procedure

3-Hydroxy-5-iodo-3-phenyl-1,3-dihydro-indol-2-one (130 mg, 0.370 mmol), 3,5-dimethyl-4-isoxazolylboronic acid (104 mg, 0.740 mmol), sodium carbonate (108 mg, 1.025 mmol), Pd(dppf)Cl2 (57 mg, 78 mmol) and lithium chloride (114.5 mg, 2.700 mmol) are added to a microwave vial. Dioxane/water (2:1, 3 mL) is added. The mixture is flushed with argon and the vessel heated at 130° C. for 1 h. The reaction mixture is diluted with water and dcm then extracted with dcm. The organic layer is dried with Na2SO4, filtered and concentrated under reduced pressure. The residue is dissolved in DMSO, filtered and purified with the acidic (formic acid) RP HPLC system. The product containing fractions are concentrated under reduced pressure. Dissolved in DMSO, aliquoted and freeze dried. Once more freeze dried with acetonitril: water. This afforded the desired product.

Workup

  1. customThe mixture is flushed with argon
  2. additionThe reaction mixture is diluted with water and dcm
  3. extractionthen extracted with dcm
  4. dry with materialThe organic layer is dried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue is dissolved in DMSO
  8. filtrationfiltered
  9. custompurified with the acidic (formic acid) RP HPLC system
  10. additionThe product containing fractions
  11. concentrationare concentrated under reduced pressure
  12. dissolutionDissolved in DMSO
  13. customfreeze dried
  14. dry with materialOnce more freeze dried with acetonitril

Sources & evidence

ORD record
ord-e0c27a533b9e4684aacc8378723e8865
Source dataset
uspto-grants-2015_08
Patent number
US09102684B2

Reaction notes

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