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

HRID 1021976Notes

Reaction equation

HRID 1021976 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[N:11]1[C:16]([NH2:17])=[CH:15][CH:14]=[CH:13][C:12]=1[NH2:18].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O1CCOCC1>[NH2:18][C:12]1[N:11]=[C:16]([NH:17][C:2]2[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=2)[CH:15]=[CH:14][CH:13]=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 48.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (20 mL), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.06 g, 4.0 mmol), pyridine-2,6-diamine (872 mg, 8.0 mmol), Pd2(dba)3 (732 mg, 0.80 mmol), XantPhos (462.4 mg, 0.80 mmol), and cesium carbonate (2.6 g, 8.0 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 1 h. After this time the reaction was cooled to room temperature. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica-gel column chromatography eluting with 20:1 ethyl acetate/methanol to afford 221a (570 mg, 48%) as a white solid. MS-ESI: [M+H]+ 295.0

Workup

  1. customA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationIt was then filtered
  5. customthe filtrate was evaporated in vacuo
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 20:1 ethyl acetate/methanol

Sources & evidence

ORD record
ord-f2cf39ad27f344c4b4e262d91f2472d0
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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