Cyanoacetamide → 4-(Methylthio)-2-oxo-6-(pyridin-3-yl)-1,2-dihydropyridine-3-carbonitrile

HRID 81071Notes

Reaction equation

HRID 81071 reaction equation
[Na].[C:2]([CH2:4][C:5]([NH2:7])=[O:6])#[N:3].[CH3:8][S:9][C:10](SC)=[CH:11][C:12]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)=O>CC(O)C>[CH3:8][S:9][C:10]1[CH:11]=[C:12]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[NH:7][C:5](=[O:6])[C:4]=1[C:2]#[N:3]

Participants

5

Reactant 3

HCID 7898CyanoacetamideHCID 5360545Sodium2×HCID 103763763,3-Bis(methylsulfanyl)-1-(pyridin-3-yl)prop-2-en-1-one

Product 1

HCID 122302154-(Methylthio)-2-oxo-6-(pyridin-3-yl)-1,2-dihydropyridine-3-carbonitrileYield 83%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

Sodium (0.408 g, 17.75 mmol) was added to 2-propanol (100 mL) and the mixture was stirred at room temperature under nitrogen for 24 h. Additional sodium (0.25 g) was added. After 17 h at room temperature, the mixture was heated to 60° C. for 1 h to dissolve the rest of the Na metal and then cooled to room temperature. 2-Cyanoacetamide (2.15 g, 25.6 mmol) was added. After 30 min at room temperature, 3,3-bis(methylthio)-1-(pyridin-3-yl)prop-2-en-1-one (5.7124 g, 25.4 mmol) was added. The mixture was stirred at room temperature for 30 min, at reflux for 2 h, and concentrated. The solid residue was dissolved in water (100 mL) and acidified with aqueous HCl (0.3 N, 100 mL) to give a suspension. The brown solid was collected by filtration and dried under vacuum to give 4-(methylthio)-2-oxo-6-(pyridin-3-yl)-1,2-dihydropyridine-3-carbonitrile (5.1267 g, 83% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.68 (1H, br. s), 9.03 (1H, s), 8.74 (1H, dd, J=4.77, 1.51 Hz), 8.24 (1H, δ, J=8.03 Hz), 7.59 (1H, dd, J=8.03, 4.77 Hz), 6.70 (1H, br. s), 2.71 (3H, s); MS (ES+) m/z: 244 (M+H); LC retention time: 1.912 min (analytical HPLC Method A).

Workup

  1. waitAfter 17 h at room temperature
  2. temperaturethe mixture was heated to 60° C. for 1 h
  3. temperaturecooled to room temperature
  4. waitAfter 30 min at room temperature
  5. stirringThe mixture was stirred at room temperature for 30 min
  6. temperatureat reflux for 2 h
  7. concentrationconcentrated
  8. dissolutionThe solid residue was dissolved in water (100 mL)
  9. customto give a suspension
  10. filtrationThe brown solid was collected by filtration
  11. customdried under vacuum

Sources & evidence

ORD record
ord-a4c29960086d4f63b8e329c9b7ef502b
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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