2-Amino-3-methylpyridine → 4-(8-Methylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 1010879Notes

Reaction equation

HRID 1010879 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.[NH2:24][C:25]1[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][N:26]=1>O1CCOCC1.O>[CH3:31][C:30]1[C:25]2[N:26]([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:24]=2)[CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 153472-Amino-3-methylpyridineHCID 67184N-bromobutanimideHCID 468638944-[(1Z)-2-ethoxyethenyl]-2-(methylthio)-5-Pyrimidinecarbonitrile

Product 1

HCID 673147444-(8-Methylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrileYield 31.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

10 g of 4-[(Z)-2-ethoxyvinyl]-2-(methylthio)-5-pyrimidinecarbonitrile (synthesized according to the method disclosed in International Publication WO2006/025567, pages 90-91) was dissolved in a mixed solvent of 150 mL of 1,4-dioxane and 30 mL of water and then 8.04 g of N-bromosuccinimide was added thereto under an ice-cold condition, and the mixture was stirred for 1.5 hours at room temperature. To the reaction solution, 4.89 g of 2-amino-3-picoline was added, and the mixture was further stirred for 2.5 hours. 200 mL of water was added to the reaction solution to extract with 2 L of a mixed solvent of chloroform and methanol (mixing ratio: 9/1). The organic layer was washed with water, and dried over anhydrous magnesium sulfate. Thereafter, the insolubles were filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in a small amount of chloroform and solidified with hexane to obtain 4.02 g of 4-(8-methylimidazo[1,2-a]pyridin-3-yl)-2-(methylthio)pyrimidine-5-carbonitrile [1-6] (hereinafter, referred to as the compound [1-6]) as a light brown solid.

Workup

  1. stirringthe mixture was further stirred for 2.5 hours
  2. extractionto extract with 2 L of a mixed solvent of chloroform and methanol (mixing ratio: 9/1)
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationThereafter, the insolubles were filtered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe resulting residue was dissolved in a small amount of chloroform

Sources & evidence

ORD record
ord-9499de2276c34e8599f9ca8c23ebfdd3
Source dataset
uspto-grants-2011_07
Patent number
US07977336B2

Reaction notes

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