A mixture of 5-isobutyl-4-propylisoxazole-3-carboxylic acid, and 4-isobutyl-5-propylisoxazole-3-carboxylic acid (42.26 mg, 0.2 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (61.1 mg, 0.200 mmol), HOBt (38.3 mg, 0.250 mmol), diisopropylethylamine (0.070 mL, 0.400 mmol) and EDC (47.9 mg, 0.250 mmol) in DMF (1 mL) was stirred at rt for 18 hr. DMF (1 mL) was added and the reaction mixture was warmed to 50° C. for 8 hr. The reaction mixture was partitioned between EtOAc (30 ml) and saturated sodium bicarbonate solution (30 ml). The organic layer was washed with water (2×30 ml) and brine (30 ml). After drying (MgSO4) and filtration, the organic layer was concentrated to afford an oil that was chromatographed on a 4 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The pure fractions were concentrated to afford a mixture of tert-butyl 1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (32 mg, 0.067 mmol, 66.6% yield) and tert-butyl 1-(4-(5-(4-isobutyl-5-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (32 mg, 0.067 mmol, 66.6% yield) as a colorless oil. HPLC retention time=1.89 minutes (YMC Combi 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1 TFA a 2 minute gradient.
