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

HRID 1921367Notes

Reaction equation

HRID 1921367 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[C:8]([CH3:17])=[N:9][C:10]([O:15]C)=[C:11]([CH2:13][CH3:14])[CH:12]=2)=[N:5][C:4]([CH3:18])=[N:3]1.[I-].[Na+].Cl[Si](C)(C)C>C(#N)C>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[C:11]([CH2:13][CH3:14])[C:10](=[O:15])[NH:9][C:8]=2[CH3:17])=[N:5][C:4]([CH3:18])=[N:3]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 6397Chlorotrimethylsilane2×HCID 674925303-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methylpyridine

Product 1

HCID 1354384515-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-3-ethyl-6-methyl-1H-pyridin-2-oneYield 66%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 3-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methylpyridine (76 mg, 0.309 mmol) and sodium iodide (139 mg, 0.927 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (5 mL) followed by drop-wise addition of chlorotrimethylsilane (116 μL, 0.924 mmol). The reaction mixture is stirred at 60° C. under nitrogen for 12 hr. LC/MS shows the reaction is incomplete. A further amount of chlorotrimethylsilane (100 μL) is added and the reaction is reheat at 60° C. for 9 hr. The reaction mixture is allowed to cool and then quenched with water (0.7 mL). After stirring for 30 min the mixture is partitioned between water and dichloromethane and the mixture treated with little sodium bisulfite to decolorize. The dichloromethane layer is separated and the aqueous layer is extracted with six further portions of dichloromethane. The combined dichloromethane 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 (1:0, increasing to 19:1). Fractions containing the product are combined, the solvent evaporated and triturated with ether to give 5-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-3-ethyl-6-methyl-1H-pyridin-2-one (47 mg, 66% yield) as a cream solid. LC/MS: RT: 1.88 min, MS: m/e=233 (M+H); 1H NMR (400 MHz, d6-DMSO, δ, ppm): 11.85 (1H, s), 7.20 (1H, s), 3.61 (3H, s), 2.36 (2H, q), 2.20 (3H, s), 2.07 (3H, s), 1.07 (3H, t).

Workup

  1. waitthe reaction is reheat at 60° C. for 9 hr
  2. temperatureto cool
  3. customquenched with water (0.7 mL)
  4. stirringAfter stirring for 30 min the mixture
  5. customis partitioned between water and dichloromethane
  6. additionthe mixture treated with little sodium bisulfite
  7. customThe dichloromethane layer is separated
  8. extractionthe aqueous layer is extracted with six further portions of dichloromethane
  9. dry with materialThe combined dichloromethane layer is dried over magnesium sulfate
  10. customevaporated
  11. customThe crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (1:0, increasing to 19:1)
  12. additionFractions containing the product
  13. customthe solvent evaporated
  14. customtriturated with ether

Sources & evidence

ORD record
ord-0950c66f69594e5f93b4f5420e6d91da
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

Loading…