Methylhydrazine → 3-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methylpyridine

HRID 1921366Notes

Reaction equation

HRID 1921366 reaction equation
C[N:2](C)[C:3](=[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])[CH3:4].[CH3:20][NH:21]N>C(O)(=O)C>[CH3:20][N:21]1[C:6]([C:7]2[C:8]([CH3:17])=[N:9][C:10]([O:15][CH3:16])=[C:11]([CH2:13][CH3:14])[CH:12]=2)=[N:5][C:3]([CH3:4])=[N:2]1

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 67492454N-(1-dimethylaminoethylidene)-5-ethyl-6-methoxy-2-methylnicotinamide

Product 1

HCID 674925303-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methylpyridineYield 57.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

In a round bottom flask under a nitrogen atmosphere N-(1-dimethylaminoethylidene)-5-ethyl-6-methoxy-2-methyl-nicotinamide (synthesized on 0.567 mmol scale) prepared in accordance with the procedures of Step 1, Example 19 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 (99:1). 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 (199:1). Fractions containing the product are combined and the solvent evaporated to give 3-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methyl-pyridine (80 mg, 57% yield). MS: m/e 247 (M+H); 1H NMR (CDCl3, δ, ppm): 7.29 (1H, s), 3.98 (3H, s), 3.66 (3H, s), 2.58 (2H, q), 2.42 (3H, s), 2.31 (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 (99:1)
  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 (199:1)
  6. additionFractions containing the product
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-5d7787fc008943249bd4e726c76e3f66
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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