2-Amino-6-methylpyridine → 6-Methyl-N-(6-methyl-2-pyridyl)pyridin-2-amine

HRID 1970705Notes

Reaction equation

HRID 1970705 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.Br[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=1.CC(C)([O-])C.[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[CH3:1][C:2]1[N:7]=[C:6]([NH:8][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 157652-Amino-6-methylpyridineHCID 792052-Bromo-6-methylpyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 30210056-Methyl-N-(6-methyl-2-pyridyl)pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Procedure

To a flask were added 0.76 g 6-methyl-2-aminopyridine, 1.0 g 2-bromo-6-methylpyridine, 0.95 g sodium tert-butoxide, 0.16 g 1,1′-bis(diphenylphosphino)ferrocene and 50 ml toluene. The mixture was purged thoroughly with nitrogen and 0.14 g of tris(dibenzylideneacetone)d2-propanollladium (0) was added and the mixture was heated to 80 C under nitrogen for 3 hours. After cooling to 22 C and quenching with 50 ml water, the product was extracted twice with ethyl acetate and washed twice with water. After filtration and solvent removal, the product was dissolved in 50 ml tert-butyl methyl ether and extracted into 60 ml 1M hydrochloric acid. Methanol was added and the mixture was heated to dissolve the solids and the organic layer was removed. The aqueous layer was basified with 3M sodium hydroxide solution, the product was extracted with tert-butyl methyl ether and washed with water. Following removal of solvent, an oil was obtained that was carried directly into the next step.

Workup

  1. customThe mixture was purged thoroughly with nitrogen and 0.14 g of tris(dibenzylideneacetone)d2-propanollladium (0)
  2. additionwas added
  3. temperaturethe mixture was heated to 80 C under nitrogen for 3 hours
  4. temperatureAfter cooling to 22 C
  5. customquenching with 50 ml water
  6. extractionthe product was extracted twice with ethyl acetate
  7. washwashed twice with water
  8. filtrationAfter filtration and solvent removal
  9. dissolutionthe product was dissolved in 50 ml tert-butyl methyl ether
  10. extractionextracted into 60 ml 1M hydrochloric acid
  11. additionMethanol was added
  12. temperaturethe mixture was heated
  13. dissolutionto dissolve the solids
  14. customthe organic layer was removed
  15. extractionthe product was extracted with tert-butyl methyl ether
  16. washwashed with water
  17. customremoval of solvent
  18. customan oil was obtained

Sources & evidence

ORD record
ord-042e28561b584224ad464a8d56effbac
Source dataset
uspto-grants-2013_04
Patent number
US08431045B2

Reaction notes

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