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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence