Nitrogen → HCID 59234644, compound

HRID 1697855Notes

Reaction equation

HRID 1697855 reaction equation
Br[C:2]1[C:3](=[O:13])[N:4]([CH2:8][CH2:9][CH2:10][CH2:11][Cl:12])[CH:5]=[CH:6][CH:7]=1.[CH3:14][C:15]1[N:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.N#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:12][CH2:11][CH2:10][CH2:9][CH2:8][N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:18]2[CH:19]=[N:20][C:15]([CH3:14])=[CH:16][CH:17]=2)[C:3]1=[O:13]

Participants

7

Reactant 4

HCID 947NitrogenHCID 11776Triphenylphosphine2×HCID 27630812-Methylpyridine-5-boronic acid2×HCID 59234646HCID 59234646, compound

Product 1

HCID 59234644HCID 59234644, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-1-(4-chlorobutyl)-2(1H)-pyridinone (400 mg, 1.51 mmol and then 627 mg, 4.54 mmol) was added to a solution of (6-methyl-3-pyridinyl)boronic acid (commercial Synchem OHG product list) (311 mg, 2.27 mmol) in dioxane (5K2CO3 ml). The mixture was degassed bubbling with N2 for 10′ and then triphenylphosphine (120 mg, 0.45 mmol) and palladium(II)acetate (34 mg, 0.15 mmol) were added. The reaction mixture was stirred at reflux for 5 h and then at room temperature for 18 hours. Further (6-methyl-3-pyridinyl)boronic acid (Synchem OHG product list) (60 mg, 0.43 mmol), triphenylphosphine (78 mg, 0.3 mmol) and palladium(II)acetate (22 mg, 0.1 mmol) were added and the reaction was stirred for additional 4 hours at 80° C. The reaction was cooled and concentrated by removing the solvent under reduced pressure. Water was added to the crude and the organic layers were extracted with DCM. The organic layers were combined, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with a gradient of methanol in DCM (from 0 to 5%) to afford the title compound (280 mg, 67%).

Workup

  1. customThe mixture was degassed
  2. additionwere added
  3. temperatureat reflux for 5 h
  4. stirringthe reaction was stirred for additional 4 hours at 80° C
  5. temperatureThe reaction was cooled
  6. concentrationconcentrated
  7. customby removing the solvent under reduced pressure
  8. additionWater was added to the crude
  9. extractionthe organic layers were extracted with DCM
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude product was purified by column chromatography on silica gel eluting with a gradient of methanol in DCM (from 0 to 5%)

Sources & evidence

ORD record
ord-bb9687bd0ae047f6aee8e9c9c2eb7f03
Source dataset
uspto-grants-2012_04
Patent number
US08163927B2

Reaction notes

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