Potassium Phosphate, Tribasic → HCID 66954743, compound

HRID 1511802Notes

Reaction equation

HRID 1511802 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.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.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH2:62]([O:69][C:70](=[O:78])[NH:71][CH:72]1[CH2:77][CH2:76][NH:75][CH2:74][CH2:73]1)[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:62]([O:69][C:70](=[O:78])[NH:71][CH:72]1[CH2:77][CH2:76][N:75]([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])[CH2:74][CH2:73]1)[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 15143044-Cbz-aminopiperidineHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 454803208-Bromo-7-fluoro-2-methoxy-1,5-naphthyridine

Product 1

HCID 66954743HCID 66954743, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
85 °C

Procedure

An oven-dried vial was charged with 8-bromo-7-fluoro-2-methoxy-[1,5]naphthyridine (797 mg, 3.40 mmol), palladium(II) acetate (31 mg, 0.136 mmol), DPEphos (146 mg, 0.272 mmol), K3PO4 (1.81 g, 8.50 mmol) and piperidin-4-yl-carbamic acid benzyl ester (875 mg, 3.40 mmol). The resulting mixture was purged with argon for several min. Dioxane (11 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 pale yellow foam (293 mg, 21%).

Workup

  1. customThe resulting mixture was purged with argon for several min
  2. additionDioxane (11 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-3936f76f53ee4b55a6068437fcc2e951
Source dataset
uspto-grants-2012_07
Patent number
US08217029B2

Reaction notes

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