Sodium Iodide → 3-ethyl-6-methyl-5-(2-methyl-2H-1,2,4-triazol-3-yl)-1H-pyridin-2-one

HRID 1921360Notes

Reaction equation

HRID 1921360 reaction equation
[CH2:1]([C:3]1[C:4]([O:16]C)=[N:5][C:6]([CH3:15])=[C:7]([C:9]2[N:10]([CH3:14])[N:11]=[CH:12][N:13]=2)[CH:8]=1)[CH3:2].[I-].[Na+].Cl[Si](C)(C)C>C(#N)C>[CH2:1]([C:3]1[C:4](=[O:16])[NH:5][C:6]([CH3:15])=[C:7]([C:9]2[N:10]([CH3:14])[N:11]=[CH:12][N:13]=2)[CH:8]=1)[CH3:2]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 674922943-ethyl-2-methoxy-6-methyl-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-pyridine

Product 1

HCID 1355256433-ethyl-6-methyl-5-(2-methyl-2H-1,2,4-triazol-3-yl)-1H-pyridin-2-oneYield 102%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-ethyl-2-methoxy-6-methyl-5-(2-methyl-2H-1,2,4-triazol-3-yl)-pyridine (76 mg, 0.328 mmol) and sodium iodide (148 mg, 0.987 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (5 mL) followed by drop-wise addition of chlorotrimethylsilane (123 μL, 0.979 mmol). The reaction mixture is stirred at 60° C. under nitrogen for 12 hr. The reaction mixture is allowed to cool and then quenched with water (0.75 mL). After stirring for 30 min, the mixture is partitioned between water and dichloromethane. The dichloromethane layer is separated and the aqueous layer is extracted with ten further portions of dichloromethane. The combined organic layer is dried over magnesium sulfate and evaporated. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (9:1). Fractions containing the product are combined and the solvent evaporated to give 3-ethyl-6-methyl-5-(2-methyl-2H-1,2,4-triazol-3-yl)-1H-pyridin-2-one (73 mg, 100% yield) as a cream solid. LC/MS: RT: 1.85 min, MS: m/e=219 (M+H); 1H NMR (400 MHz, d6-DMSO, δ, ppm): 11.92 (1H, s), 7.98 (1H, s), 3.74 (3H, s), 2.39 (2H, q), 1.09 (3H, t).

Workup

  1. temperatureto cool
  2. customquenched with water (0.75 mL)
  3. stirringAfter stirring for 30 min
  4. customthe mixture is partitioned between water and dichloromethane
  5. customThe dichloromethane layer is separated
  6. extractionthe aqueous layer is extracted with ten further portions of dichloromethane
  7. dry with materialThe combined organic layer is dried over magnesium sulfate
  8. customevaporated
  9. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (9:1)
  10. additionFractions containing the product
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-9ed6296cbe7f457b94a19396a1aa81eb
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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