Tricyclohexylphosphine → 6-Methyl-3'-nitro-4,4'-bipyridin-2-amine

HRID 69969Notes

Reaction equation

HRID 69969 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CC([O-])=O.[K+].Cl[C:53]1[CH:58]=[CH:57][N:56]=[CH:55][C:54]=1[N+:59]([O-:61])=[O:60]>O1CCOCC1.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O.CCOC(C)=O>[CH3:8][C:6]1[N:5]=[C:4]([NH2:9])[CH:3]=[C:2]([C:53]2[CH:58]=[CH:57][N:56]=[CH:55][C:54]=2[N+:59]([O-:61])=[O:60])[CH:7]=1

Participants

11

Reactant 5

HCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 27357814-Chloro-3-nitropyridineHCID 190505094-Chloro-6-methylpyridin-2-amine

Product 1

HCID 690474886-Methyl-3'-nitro-4,4'-bipyridin-2-amineYield 35%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-chloro-6-methylpyridin-2-amine (1.0 equiv.) in dioxane was added bis(pinacolato)diboron (2.0 equiv.), Pd2(dba)3 (0.05 equiv.), PCy3 (0.075 equiv.), and KOAc (3.0 equiv.). The reaction was heated for 3 hrs at 110° C., then filtered, and concentrated. The crude material was dried under vacuo, then dissolved in DME/2M Na2CO3 (3:1), 4-chloro-3-nitropyridine (2.0 equiv.) was added, followed by Pd(dppf)Cl2-DCM (0.1 equiv.). The mixture was heated to 120° C. for 1 hr, then EtOAc and H2O were added, the organic phase was removed, dried with Na2SO4, and concentrated. Purification via SiO2 column chromatography eluting with EtOAc yielded 6-methyl-3′-nitro-4,4′-bipyridin-2-amine in 35% yield. LCMS (m/z): 231.1 (MH+) LC Rt=1.47 min.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. dry with materialThe crude material was dried under vacuo
  4. dissolutiondissolved in DME/2M Na2CO3 (3:1)
  5. temperatureThe mixture was heated to 120° C. for 1 hr
  6. customthe organic phase was removed
  7. dry with materialdried with Na2SO4
  8. concentrationconcentrated
  9. customPurification via SiO2 column chromatography
  10. washeluting with EtOAc

Sources & evidence

ORD record
ord-3269d1ef57194787b68c436073fd98d9
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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