Diisopropylethylamine → 2-Ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol

Participants

Reaction Steps

To a solution of 2-isobutyl-6-methyl-isonicotinic acid hydrochloride (2.18 g, 9.53 mmol) and DIPEA (3.69 g, 28.6 mmol) in DCM (10 mL), TBTU (3.67 g, 11.44 mmol) is added. The mixture is stirred for 5 min before 3,5-diethyl-4,N-dihydroxy-benzamidine (1.85 g, 9.53 mmol) is added. The mixture is stirred at rt for 1 h. The mixture is diluted with DCM, washed with sat. aq. NaHCO3 solution, dried over MgSO4, filtered and concentrated. The crude 2-isobutyl-6-methyl-isonicotinic acid (3-ethyl-4,N-dihydroxy-5-methyl-benzamidine) ester (LC-MS: tR=0.79 min, [M+1]+=370.06) is dissolved in dioxane (50 mL) and heated to 100° C. for 4 h. The solvent is evaporated and the crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol (1.97 g) as a colourless oil; LC-MS: tR=0.93 min; [M+1]+=352.16; 1H NMR (CDCl3): δ 7.85 (s, 2 H), 7.75 (s, 1 H), 7.70 (s, 1 H), 5.05 (s br, 1H), 2.78 (d, J=7.5 Hz, 2H), 2.74 (q, J=7.5 Hz, 2H), 2.69 (s, 3H), 2.37 8 s, 3H), 2.19 (hept, J=7.5 Hz, 1H), 1.34 (t, J=7.5 Hz, 3H), 1.00 (d, J=6.5 Hz, 6H).

Provenance & Evidence