Methyl iodide → 2-(Methylthio)-4-(2-pyridinyl)pyrimidine

HRID 1410378Notes

Reaction equation

HRID 1410378 reaction equation
[O-][CH2:2]C.[Na+].[Na].CN(/[CH:9]=[CH:10]/[C:11]([C:13]1[N:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O)C.[NH2:19][C:20]([NH2:22])=[S:21].IC>[Cl-].[NH4+].O.C(O)C>[CH3:2][S:21][C:20]1[N:22]=[C:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][N:18]=2)[CH:10]=[CH:9][N:19]=1

Participants

9

Reactant 5

HCID 6328Methyl iodideHCID 2723790ThioureaHCID 2723922Sodium ethoxideHCID 5360545SodiumHCID 5369159(2E)-3-(Dimethylamino)-1-(2-pyridinyl)-2-propen-1-one

Product 1

HCID 221748622-(Methylthio)-4-(2-pyridinyl)pyrimidineYield 96%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a stirred solution of sodium ethoxide (freshly prepared from sodium metal (5.11 g, 222 mmol) and ethanol (350 mL)) was added 3-dimethylamino-1-pyridin-2-yl-propenone (28.0 g, 159 mmol) and thiourea (12.9 g, 170 mmol). The solution was heated to reflux and stirred for 3 hours. The solution was allowed to cool to room temperature, and then iodomethane (13.8 mL, 222 mmol) was added dropwise over 10 minutes. The solution was stirred at room temperature for 2 hours, and then diluted with saturated ammonium chloride solution (250 mL) and water (250 mL). The suspension was extracted with ethyl ether (200 mL×3), and the combined organic extracts washed with saturated sodium thiosulfate solution (150 mL) and brine (150 mL). The organic phase was dried (magnesium sulfate), filtered, and concentrated to provide 30.1 g (96%) of the product as a brown oil: 1H NMR (CDCl3) δ 8.70-8.69 (m, 1H), 8.64 (d, J=5.2 Hz, 1H), 8.48 (d, J=7.9 Hz, 1H), 8.01 (d, J=5.2 Hz, 1H), 7.87-7.82 (m, 1H), 7.41-7.38 (m, 1H), 2.65 (s, 3H) ppm. 13C NMR (CDCl3) δ 172.6, 163.1, 158.5, 153.9, 149.7, 137.3, 125.7, 122.0, 112.6, 14.5 ppm.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux
  3. stirringThe solution was stirred at room temperature for 2 hours
  4. extractionThe suspension was extracted with ethyl ether (200 mL×3)
  5. washthe combined organic extracts washed with saturated sodium thiosulfate solution (150 mL) and brine (150 mL)
  6. dry with materialThe organic phase was dried (magnesium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d6cd801865b549a5bd098fb34f1ab7e0
Source dataset
uspto-grants-2014_12
Patent number
US08921547B2

Reaction notes

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