N-bromobutanimide → 4-(8-Ethylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 1010889Notes

Reaction equation

HRID 1010889 reaction equation
C(O/[CH:4]=[CH:5]\[C:6]1[C:11]([C:12]#[N:13])=[CH:10][N:9]=[C:8]([S:14][CH3:15])[N:7]=1)C.BrN1C(=O)CCC1=O.[CH2:24]([C:26]1[C:27]([NH2:32])=[N:28][CH:29]=[CH:30][CH:31]=1)[CH3:25].C(=O)([O-])O.[Na+]>O1CCOCC1.O>[CH2:24]([C:26]1[C:27]2[N:28]([C:5]([C:6]3[C:11]([C:12]#[N:13])=[CH:10][N:9]=[C:8]([S:14][CH3:15])[N:7]=3)=[CH:4][N:32]=2)[CH:29]=[CH:30][CH:31]=1)[CH3:25]

Participants

7

Reactant 4

HCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 110516363-Ethylpyridin-2-amineHCID 468638944-[(1Z)-2-ethoxyethenyl]-2-(methylthio)-5-Pyrimidinecarbonitrile

Product 1

HCID 673141654-(8-Ethylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrileYield 68.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4.89 g of 4-[(Z)-2-ethoxyvinyl]-2-(methylthio)-5-pyrimidinecarbonitrile (synthesized according to the method disclosed in International Publication WO2006/025567, page 90 to 91) was dissolved in a mixed solvent of 50 mL of 1,4-dioxane and 5 mL of water, then 3.93 g of N-bromosuccinimide was added under an ice-cold condition, and the mixture was stirred for 1 hour at room temperature. To the reaction solution was added 2.7 g of 3-ethylpyridine-2-amine (synthesized according to the method disclosed in International Publication WO2006/025567, page 142), and the solution was stirred overnight at room temperature. To the reaction solution was added a saturated aqueous solution of sodium hydrogen carbonate, the solution was extracted with chloroform, and the resulting organic layer was dried over anhydrous sodium sulfate. The insolubles were filtered, and the filtrate was concentrated under reduced pressure. Diethylether was added to the resulting residue, and the resultant solution was stirred for 3 hours. Thus produced solid was taken by filtration and dried under reduced pressure to obtain 4.46 g of 4-(8-ethylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile [5-6] (hereinafter, referred to as the compound [5-6]) as a pale yellow solid.

Workup

  1. customsynthesized
  2. stirringwas stirred overnight at room temperature
  3. extractionthe solution was extracted with chloroform
  4. dry with materialthe resulting organic layer was dried over anhydrous sodium sulfate
  5. filtrationThe insolubles were filtered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. additionDiethylether was added to the resulting residue
  8. stirringthe resultant solution was stirred for 3 hours
  9. filtrationThus produced solid was taken by filtration
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-4c0f6bbcfbb1453aacc8273cc0d29b9f
Source dataset
uspto-grants-2011_07
Patent number
US07977336B2

Reaction notes

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