2-Bromopyridine → HCID 21620216, compound

HRID 1446656Notes

Reaction equation

HRID 1446656 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.Br[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCOCC1>[N:55]1[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=1[C:2]1[CH:7]=[CH:6][N:5]2[CH:8]=[CH:9][N:10]=[C:4]2[CH:3]=1

Participants

12

Reactant 7

HCID 79732-BromopyridineHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 196959017-Chloroimidazo(1,2-a)pyridine

Product 1

HCID 21620216HCID 21620216, compoundYield 111%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a round bottomed flask add 7-chloro-imidazo[1,2-a]pyridine (0.25 g, 1.6 mmol), tricyclohexylphosphine (55 mg, 0.12 equiv.), potassium acetate (0.24 g, 1.5 equiv.), bis(pinacolato)diboron (0.46 g, 1.1 equiv.) and dioxane (10 mL). Deoxygenate this mixture thoroughly with N2 then add tris(dibenzylideneacetone)dipalladium (0) (75 mg, 0.05 equiv.) and heat the reaction to 80° C. overnight under N2. Filter the reaction thru Celite® and wash with DCM then concentrate to dryness. To this residue, add 2-bromopyridine (0.14 mL, 1.5 mmol), S-Phos (75 mg, 0.125 equiv.), potassium phosphate (0.62 g, 2 equiv.), dioxane (10 mL), and water (5 mL). Deoxygenate this mixture thoroughly with N2, add palladium (II) acetate (16 mg, 0.05 equiv.), and reflux the reaction overnight. Concentrate the reaction to dryness and slurry in DCM. Filter this slurry thru Celite® and wash with DCM. Concentrate the filtrate then purify by silica column (EtOAc to 5% MeOH: DCM) to give a residue (0.325 g, >100%). MS (ES), m/z 196 (M+1).

Workup

  1. customDeoxygenate this mixture thoroughly with N2
  2. customthe reaction to 80° C. overnight under N2
  3. filtrationFilter the reaction thru Celite®
  4. washwash with DCM
  5. concentrationthen concentrate to dryness
  6. customDeoxygenate this mixture thoroughly with N2
  7. temperaturereflux
  8. customthe reaction overnight
  9. concentrationConcentrate
  10. customthe reaction to dryness and slurry in DCM
  11. filtrationFilter this slurry thru Celite®
  12. washwash with DCM
  13. concentrationConcentrate the filtrate
  14. customthen purify by silica column (EtOAc to 5% MeOH: DCM)

Sources & evidence

ORD record
ord-e6eb77255f4248b98e6fc945d9f3a036
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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