Hydrazine hydrate (1:1) → 3-ethyl-2-methoxy-6-methyl-5-(5-methyl-1H-1,2,4-triazol-3-yl)pyridine

HRID 1921368Notes

Reaction equation

HRID 1921368 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].O.[NH2:21]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:5]=[C:3]([CH3:4])[NH:2][N:21]=2)[CH:12]=1)[CH3:14]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67492454N-(1-dimethylaminoethylidene)-5-ethyl-6-methoxy-2-methylnicotinamide

Product 1

HCID 674921003-ethyl-2-methoxy-6-methyl-5-(5-methyl-1H-1,2,4-triazol-3-yl)pyridineYield 80%

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 hydrazine hydrate (36 μL, 0.742 mmol). The resulting mixture is stirred at 90° C. for 12 hr. The reaction mixture is evaporated 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-(5-methyl-1H-1,2,4-triazol-3-yl)pyridine (105 mg, 80% yield, 2 steps) as a orange-red. MS: m/e=233 (M+H); 1H NMR (CDCl3, δ, ppm): 9.8-11.6 (1H, br.s), 7.81 (1H, s), 3.97 (3H, s), 2.69 (3H, s), 2.59 (2H, q), 2.52 (3H, s), 1.19 (3H, t).

Workup

  1. customThe reaction mixture is evaporated
  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-1f20aff31c1e4c15a17fc12b689ac480
Source dataset
uspto-grants-2012_05
Patent number
US08173682B2

Reaction notes

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