Potassium Phosphate, Tribasic → HCID 67290561, compound

HRID 511858Notes

Reaction equation

HRID 511858 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:4][CH:3]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CO>[CH:27]1([C:2]2[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]([NH:10][C@@H:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])=[CH:15][N:14]=3)[CH3:12])=[O:9])=[CH:4][CH:3]=2)[CH2:29][CH2:28]1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 49792855(R)-2-(4-bromophenoxy)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide

Product 1

HCID 67290561HCID 67290561, compoundYield 7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (R)-2-(4-bromophenoxy)-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)acetamide (100 mg, 0.23 mmol) and cyclopropylboronic acid (26 mg, 0.30 mmol) in dioxane (2 mL) were added 1.27 M potassium phosphate (0.36 mL) and tetrakistriphenyl phosphine palladium (13 mg, 0.012 mmol) at room temperature. The mixture was stirred at 120° C. using microwave oven for 2 hours. The mixture was dried over magnesium sulfate. After the filtration to separate solvent and magnesium sulfate, the solvent was removed under reduced pressure to give the residue. The residue was diluted with methanol and applied onto a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.), and the solid phase matrix was rinsed with methanol (6 mL). The crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL) and concentrated in vacuo. The residue was purified by preparative LC-MS to give 6.5 mg, (7% yield) of the title compound.

Workup

  1. customfor 2 hours
  2. dry with materialThe mixture was dried over magnesium sulfate
  3. filtrationAfter the filtration
  4. customto separate solvent and magnesium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customto give the residue
  7. wash), and the solid phase matrix was rinsed with methanol (6 mL)
  8. washThe crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by preparative LC-MS

Sources & evidence

ORD record
ord-40b9179661d34e5e831b2644fd65b951
Source dataset
uspto-grants-2015_08
Patent number
US09101616B2

Reaction notes

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