Cesium carbonate → 5-Bromo-3-(imidazo[1,2-a]pyrimidin-7-ylamino)-1-methylpyridin-2(1H)-one

HRID 1021910Notes

Reaction equation

HRID 1021910 reaction equation
[N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][C:7]([NH2:10])=[N:6][C:5]=12.Br[C:12]1[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=[C:16]([Br:18])[CH:17]=1.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>[Br:18][C:16]1[CH:17]=[C:12]([NH:10][C:7]2[CH:8]=[CH:9][N:4]3[CH:3]=[CH:2][N:1]=[C:5]3[N:6]=2)[C:13](=[O:20])[N:14]([CH3:19])[CH:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 23000364Imidazo[1,2-A]pyrimidin-7-amine

Product 1

HCID 866843685-Bromo-3-(imidazo[1,2-a]pyrimidin-7-ylamino)-1-methylpyridin-2(1H)-oneYield 31%

Reagents, catalysts & solvents 2

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

Procedure

A 250-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 199a (2.2 g, 16.4 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (8.77 g, 32.8 mmol), Pd2dba3 (1.5 g, 1.64 mmol), Xantphos (1.88 g, 3.28 mmol), Cs2CO3 (10.7 g. 32.8 mmol), and 1,4-dioxane (150 mL). The system was evacuated and then refilled with N2. It was then heated at reflux for 3 h. After the completion of the reaction, the mixture was filtered off and the solid was washed with methanol (60 mL). The combined filtrate was evaporated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 199b as a light green solid (1.63 g, 31%). MS: [M+H]+ 320.1

Workup

  1. customA 250-mL round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then heated
  5. temperatureat reflux for 3 h
  6. customAfter the completion of the reaction
  7. filtrationthe mixture was filtered off
  8. washthe solid was washed with methanol (60 mL)
  9. customThe combined filtrate was evaporated under reduced pressure
  10. customthe residue was purified by silica-gel column chromatography
  11. washeluting with 20:1 dichloromethane/methanol

Sources & evidence

ORD record
ord-ffd64388bbf345aeb0348cfc9c67ccf6
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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