2,6-Diaminopyridine → 3-(6-Amino-pyridin-2-ylamino)-5-bromo-1-methyl-1H-pyridin-2-one

HRID 557524Notes

Reaction equation

HRID 557524 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[N:3]=1.Br[C:10]1[C:11](=[O:18])[N:12]([CH3:17])[CH:13]=[C:14]([Br:16])[CH:15]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[NH2:8][C:4]1[N:3]=[C:2]([NH:1][C:10]2[C:11](=[O:18])[N:12]([CH3:17])[CH:13]=[C:14]([Br:16])[CH:15]=2)[CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 88612,6-DiaminopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-one

Product 1

HCID 597406173-(6-Amino-pyridin-2-ylamino)-5-bromo-1-methyl-1H-pyridin-2-oneYield 18.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with 2,6-diaminopyridine (0.27 g, 1.2 mmol), 3,5-dibromo-1-methyl-1H-pyridin-2-one (1) (0.27 g, 1 mmol), Pd2(dba)3 (0.046 g, 0.05 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.089 g, 0.15 mmol), and Cs2CO3 (0.49 g, 1.5 mmol) in dioxane (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (10 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-10%, MeOH in dichlormethane/Ether (1/1), to give 0.054 g (18%) of 3-(6-amino-pyridin-2-ylamino)-5-bromo-1-methyl-1H-pyridin-2-one (2) as a solid.

Workup

  1. customA 48-mL sealed tube
  2. customequipped with a magnetic stirring bar
  3. customAfter the mixture was degassed for 15 min.
  4. temperatureThen, the reaction mixture was cooled to room temperature
  5. additionpoured into H2O (10 mL)
  6. additionTo this was added dichloromethane (10 mL)
  7. customthe layers were separated
  8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
  9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude mixture was purified by column chromatography, gradient 0-10%, MeOH in dichlormethane/Ether (1/1)

Sources & evidence

ORD record
ord-0a62680799064e80b56fd42ab4f59116
Source dataset
uspto-grants-2011_11
Patent number
US08058446B2

Reaction notes

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