Potassium Phosphate, Tribasic → HCID 66953575, compound

HRID 1511787Notes

Reaction equation

HRID 1511787 reaction equation
Br[C:2]1[C:3]([F:14])=[CH:4][N:5]=[C:6]2[C:11]=1[N:10]=[C:9]([O:12][CH3:13])[CH:8]=[CH:7]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:23]([O:30][C:31](=[O:37])[NH:32][CH:33]1[CH2:36][NH:35][CH2:34]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:23]([O:30][C:31](=[O:37])[NH:32][CH:33]1[CH2:36][N:35]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=3)[N:5]=[CH:4][C:3]=2[F:14])[CH2:34]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 17750122Benzyl azetidin-3-ylcarbamateHCID 454803208-Bromo-7-fluoro-2-methoxy-1,5-naphthyridine

Product 1

HCID 66953575HCID 66953575, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherCatalyst

Conditions

Temperature
85 °C

Procedure

An oven-dried vial was charged with 8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (commercial; 2.0 g, 7.78 mmol), palladium(II) acetate (70 mg, 0.31 mmol), DPEphos (335 mg, 0.62 mmol), K3PO4 (4.13 g, 19.45 mmol) and azetidin-3-yl-carbamic acid benzyl ester (1.68 g, 8.17 mmol). The resulting mixture was purged with argon for several min. Dioxane (25 mL) was then added via syringe and the resulting suspension was purged with argon for 3 min. The mixture was then heated at 85° C. overnight. The solvent was removed in vacuo and the residue was extracted with EA/water. The org. layer was washed with brine, dried over MgSO4 and concentrated. To the resulting solid TBME and a few drops of DCM and MeOH were added and the mixture was sonicated for 5 min and filtered to afford the title intermediate as a beige solid (2.53 g, 85%).

Workup

  1. customThe resulting mixture was purged with argon for several min
  2. additionDioxane (25 mL) was then added via syringe
  3. customthe resulting suspension was purged with argon for 3 min
  4. customThe solvent was removed in vacuo
  5. extractionthe residue was extracted with EA/water
  6. washlayer was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. additionTo the resulting solid TBME and a few drops of DCM and MeOH were added
  10. customthe mixture was sonicated for 5 min
  11. filtrationfiltered

Sources & evidence

ORD record
ord-b88317b9b7a14fb7922fde8e412a06bd
Source dataset
uspto-grants-2012_07
Patent number
US08217029B2

Reaction notes

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