Hydrochloric Acid → 1-(2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl)-azetidine-3-carboxylic acid

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Reaction Steps

A solution of methanesulfonic acid 2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-ethyl ester (300 mg, 633 μmol), azetidine-3-carboxylic acid methyl ester (218 mg, 1.84 μmol) and triethylamine (129 mg, 1.26 mmol) in ethanol (10 mL) is stirred in a sealed vial at 80° C. for 96 h. The mixture is cooled to rt, diluted with 3 M aq. NaOH and again stirred at rt for 1 h. The mixture is acidified by adding aq. HCl and is then extracted with EA (2×25 mL). The org. extracts are combined, dried over MgSO4, filtered and concentrated. The crude product is purified by prep. HPLC to give the title compound (170 mg) as a colourless oil; LC-MS: tR=0.90 min, [M+H]+=479.10; 1H NMR (CDCl3): δ0.98 (d, J=6.5 Hz, 6H), 1.282 (t, J=7.0 Hz, 3H), 1.93 (hept, J=7.0 Hz, 1H), 2.38 (s, 3H), 2.45 (s, 3H), 2.61 (d, J=7.3 Hz, 2H), 2.73 (q, J=7.3 Hz, 2H), 3.71-3.82 (m, 2H), 3.97-4.08 (m, 1H), 4.19-4.27 (m, 2H), 4.37-4.62 (m, 2H), 4.73-4.97 (m, 2H), 7.87 (s, 1H), 7.89 (s, 1H), 8.07 (s, 1H), 8.53 (s, 1H).

Provenance & Evidence