Pyridine → HCID 11629954, compound

HRID 1921371Notes

Reaction equation

HRID 1921371 reaction equation
[C:1](Cl)(=O)C.[CH2:5]([C:7]1[C:8]([O:18]C)=[N:9][C:10]([CH3:17])=[C:11]([CH:16]=1)[C:12](NO)=N)C.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH3:17][C:10]1[NH:9][C:8](=[O:18])[C:7]([CH3:5])=[CH:16][C:11]=1[C:12]1[CH:1]=[C:24]([CH:23]=[CH:22][CH:21]=1)[C:25]#[N:20]

Participants

4

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chloride2×HCID 178436635HCID 178436635, compound

Product 1

HCID 11629954HCID 11629954, compoundYield 20%

Conditions

Temperature
98 °C

Procedure

Acetyl chloride (121 μL, 1.70 mmol) is added drop-wise to a mixture of 5-ethyl-N-hydroxy-6-methoxy-2-methylnicotinamidine (formed on 1.705 mmol scale) in pyridine (5 mL) under a nitrogen atmosphere. After the vigorous reaction has ceased, the mixture is heated at 98° C. for 22 hr. LC/MS indicates the reaction is incomplete and a further amount of acetyl chloride (50 μL) is added and the reaction mixture is heated for an additional 40 min. The reaction mixture is allowed to cool, then evaporated to dryness. The residue is suspended in water and extracted with three portions of ethyl acetate. The combined ethyl acetate layer is washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and evaporated to leave a sticky, orange residue. The residue is extracted with five portions of heptane and the combined extract is evaporated. The residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with heptane:dichloromethane (9:1, increasing to 4:1). Clean fractions containing the product are combined and the solvent evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(5-methyl-1,2,4-oxadiazol-3-yl)pyridine (47 mg, 20% combined yield from Steps 3 and 4) as an off-white solid. MS: m/e=234 (M+H); 1H NMR (CDCl3, δ, ppm): 7.94 (1H, s), 4.00 (3H, s), 2.74 (3H, s), 2.64 (3H, s), 2.60 (2H, q), 1.10 (3H, t).

Workup

  1. customAfter the vigorous reaction
  2. temperaturethe reaction mixture is heated for an additional 40 min
  3. temperatureto cool
  4. customevaporated to dryness
  5. extractionextracted with three portions of ethyl acetate
  6. washThe combined ethyl acetate layer is washed with saturated aqueous sodium bicarbonate
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto leave a sticky, orange residue
  11. extractionThe residue is extracted with five portions of heptane
  12. extractionthe combined extract
  13. customis evaporated
  14. customThe residue is purified by flash chromatography on a 10-gram silica gel cartridge by elution with heptane:dichloromethane (9:1, increasing to 4:1)
  15. additionClean fractions containing the product
  16. customthe solvent evaporated

Sources & evidence

ORD record
ord-3ad57edcbe8c446db59ec5e19502b6bf
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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