Methylhydrazine → 3-ethyl-2-methoxy-6-methyl-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-pyridine

HRID 1921359Notes

Reaction equation

HRID 1921359 reaction equation
C[N:2]([CH:4]=[N:5][C:6](=O)[C:7]1[CH:12]=[C:11]([CH2:13][CH3:14])[C:10]([O:15][CH3:16])=[N:9][C:8]=1[CH3:17])C.[CH3:19][NH:20]N>C(O)(=O)C>[CH2:13]([C:11]1[C:10]([O:15][CH3:16])=[N:9][C:8]([CH3:17])=[C:7]([C:6]2[N:20]([CH3:19])[N:2]=[CH:4][N:5]=2)[CH:12]=1)[CH3:14]

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 67492560N-dimethylaminomethylene-5-ethyl-6-methoxy-2-methylnicotinamide

Product 1

HCID 674922943-ethyl-2-methoxy-6-methyl-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-pyridineYield 61%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

In a round bottom flask under a nitrogen atmosphere N-dimethylaminomethylene-5-ethyl-6-methoxy-2-methyl-nicotinamide (synthesized on 0.567 mmol scale) of Step 2, Example 16 is treated with glacial acetic acid (1 mL) followed by methylhydrazine (50 μL, 0.94 mmol). The resulting mixture is stirred at 90° C. for 12 hr. The reaction mixture is evaporated to dryness and the residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1). Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (99:1). Fractions containing the product are combined and the solvent evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-pyridine (80 mg, 61% yield) as a light yellow oil. MS: m/e=233 (M+H); 1H NMR (δ, ppm): 7.96 (1H, s), 7.29 (1H, s), 3.99 (3H, s), 3.74 (3H, s), 2.59 (2H, q), 2.30 (3H, s), 1.19 (3H, t).

Workup

  1. customThe reaction mixture is evaporated to dryness
  2. customthe residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1)
  3. additionFractions containing the product
  4. customevaporated
  5. customre-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (99:1)
  6. additionFractions containing the product
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-e0aff15e39114012b72b38ca06be45e8
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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