Diisopropylethylamine → 3-(3-Amino-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptane

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DIEA (2.0 to 2.2 eq) and HATU (1.0 to 1.1 eq) were added into a solution of the carboxylic acid derivative (1 eq) in anhydrous DMF (4 mL/mmol of carboxylic acid derivative) cooled at 0° C. The resulting mixture was stirred at 0° C. for a period of 5 to 30 minutes. Then the amidoxime derivative (1.0 to 1.2 eq) was added neat or as a DMF solution (2 mL/mmol of amidoxime derivative). The resulting mixture was stirred at 0° C. or RT for a period of 30 minutes to 18 hours. The reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc, and then washed with water and brine. The aqueous layers were extracted once. The organic layers were combined, dried (MgSO4 or Na2SO4) and the solvents were removed under reduced pressure. The residue was either taken up with toluene (6 mL/mmol of carboxylic acid derivative) and pyridine (2 mL/mmol of carboxylic acid derivative) or with ACN (8.5 mL/mmol of carboxylic acid derivative). The resulting mixture was heated at a temperature between 80° C. to reflux for a period of 12 to 72 hours. The reaction mixture was diluted with an adequate solvent, such as Et2O, MTBE or EtOAc, and then washed with water and brine. The aqueous layers were extracted once. The organic layers were combined, dried (MgSO4 or Na2SO4) and the solvents were evaporated under reduced pressure. Purification by flash chromatography or precipitation gave the expected oxadiazole derivative.

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