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

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Reaction Steps

To a solution of 2-isobutyl-6-methyl-isonicotinic acid hydrochloride (41 mg, 0.178 mmol) and DIPEA (69 mg, 0.535 mmol) in DMF (2 mL) is added TBTU (57 mg, 0.178 mmol) at 0° C. The mixture is stirred for 30 min at 0° C. before 2-isobutyl-6-methyl-isonicotinic hydrazide (37 mg, 0.179 mmol) is added. Stirring is continued for 2 h. The mixture is diluted with ether (200 mL) and washed with 10% aq. citric acid solution (3×10 mL), sat. aq. NaHCO3-solution (3×10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated to give crude 2-isobutyl-6-methyl-isonicotinic acid N′-(2-isobutyl-6-methyl-pyridine-4-carbonyl)-hydrazide (70 mg) as a yellow oil; LC-MS: tR=0.60 min, [M+1]+=383.25. A part of this material (45 mg, 0.119 mmol) is dissolved in DCM (7 mL) and pyridine (47 mg, 0.595 mmol) followed by trifluoromethanesulfonic anhydride (37 mg, 0.131 mmol) is added at 0° C. The mixture is stirred for 2 h at 0° C. and 15 h at rt before it 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 2:3 to give 2-isobutyl-4-[2-(2-isobutyl-6-methyl-4-pyridinyl)-[1,3,4]oxadiazol-5-yl]-6-methyl-pyridine (27 mg) as a colourless oil; LC-MS: tR=0.72 min, [M+1]+=365.54; 1H NMR (CDCl3): δ 0.99 (d, J=6.5 Hz, 12H), 2.19 (hept, J=7.0 Hz, 2H), 2.68 (s, 6H), 2.77 (d, J=7.3 Hz, 4H), 7.64 (s, 2H), 7.69 (s, 2H).

Provenance & Evidence