Pyridine → 2-Ethyl-4-[2-(2-ethyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridine

Participants

Reaction Conditions

Reaction Steps

A suspension of 2-ethyl-6-methyl-isonicotinic acid (80 mg, 0.397 mmol) in SOCl2 (2 mL) is stirred at 65° C. for 1 h. The now clear solution is concentrated and dried to provide crude 2-ethyl-6-methyl-isonicotinic acid chloride. This material is dissolved in THF (4.5 mL) and treated with 1 M hydrazine in THF (1.59 mL, 1.59 mmol). The mixture is stirred at rt for 15 h before it is diluted with diethyl ether, washed with 1 M aq. HCl followed by 33% aq. KOH solution, dried over MgSO4, filtered and concentrated to give crude 2-ethyl-6-methyl-isonicotinic acid N′-(2-ethyl-6-methyl-pyridine-4-carbonyl)-hydrazide (38 mg) as a white solid; LC-MS: tR=0.47 min, [M+1]+=327.41. This material is dissolved in DCM (5 mL) and pyridine (42 mg, 0.536 mmol) followed by trifluoromethanesulfonic anhydride (91 mg, 0.322 mmol) is added at 0° C. The mixture is stirred at 0° C. for 2 h before another portion of pyridine (42 mg, 0.536 mmol) and trifluoromethanesulfonic anhydride (61 mg, 0.214 mmol) is added. Stirring is continued for 2 h. The mixture is diluted with DCM, washed with water, dried over MgSO4, filtered and the solvent of the filtrate is evaporated. The crude product is purified by prep. TLC with heptane:EA 7:3 to give 2-ethyl-4-[2-(2-ethyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridine (16 mg) as a colourless oil; LC-MS: tR=0.59 min, [M+1]+=309.13; 1H NMR (CDCl3): δ 1.39 (t, J=7.8 Hz, 6H), 2.68 (s, 6H), 2.94 (q, J=7.5 Hz, 4H), 7.70 (s, 4H).

Provenance & Evidence