1,4-Dioxane → HCID 86687560, compound

HRID 1473505Notes

Reaction equation

HRID 1473505 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.[CH2:16]([S:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28](Br)=[CH:29][CH:30]=[N:31]2)=[CH:26][N:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH2:16]([S:23][C:24]1[CH:33]=[C:32]2[C:27]([C:28]([C:4]3[CH:5]=[CH:6][C:7]([C:9]([F:12])([F:11])[F:10])=[CH:8][C:3]=3[O:2][CH3:1])=[CH:29][CH:30]=[N:31]2)=[CH:26][N:25]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687559HCID 86687559, compound

Product 1

HCID 86687560HCID 86687560, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

A screw capped vial was charged with 2-methoxy-4-(trifluoromethyl)phenyl boronic acid (0.096 g, 0.438 mmol), 7-(benzylthio)-4-bromo-1,6-naphthyridine (0.145 g, 0.438 mmol), and potassium phosphate tribasic (0.279 ml, 1.313 mmol). Dioxane (1.756 ml) and water (0.585 ml) were added and the vial was purged with argon, followed by addition of Pd(AmPhos)2Cl2 (0.019 g, 0.026 mmol). The vial was capped and heated to 110° C. After 3 hours, the reaction was cooled to room temperature, diluted with water (30 mL), and washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel MPLC chromatography (40 g), eluting with 0 to 100% ethyl acetate in heptanes. The fractions were collected and the solvent was removed under reduced pressure to provide 0.129 g of 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)-1,6-naphthyridine as an off white solid. m/z (ESI) 427.2 (M+H)+.

Workup

  1. customA screw capped vial
  2. customthe vial was purged with argon
  3. customThe vial was capped
  4. temperaturethe reaction was cooled to room temperature
  5. washwashed with ethyl acetate (20 mL×3)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting material was purified via silica gel MPLC chromatography (40 g)
  10. washeluting with 0 to 100% ethyl acetate in heptanes
  11. customThe fractions were collected
  12. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-31f09ae85ab3400f9b901c6446cdbced
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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