Condensation of the protected aniline derivative (I) with 4-cyanobenzenesulfonyl chloride (II) in the presence of pyridine afforded sulfonamide (III). Subsequent reaction of he nitrile group of (III) with hydroxylamine provided the corresponding amidoxime (IV), which was reacted with 3,4-difluorophenylacetic acid (V) and EDC to produce the oxadiazole (VI). Finally, the Boc protecting group of (VI) was removed by treatment with trifluoroacetic acid.

Condensation of the protected aniline derivative (I) with 4-cyanobenzenesulfonyl chloride (II) in the presence of pyridine afforded sulfonamide (III). Subsequent reaction of he nitrile group of (III) with hydroxylamine provided the corresponding amidoxime (IV), which was reacted with 4-(trifluoromethoxy)phenylacetic acid (V) and EDC to produce the oxadiazole (VI). Finally, the Boc protecting group of (VI) was removed by treatment with trifluoroacetic acid.

The title compound was prepared by solid-phase synthesis. Resin (II) was treated with 4-nitrophenyl chloroformate (I), and the activated nitrophenyl carbonate resin (III) was coupled to (R)-N-[2-(4-aminophenyl)ethyl]-2-hydroxy-2-(pyrid-3-yl)ethylamine (IV) to furnish the resine-bound aniline (V). After protection of the hydroxyl group as the triethylsilyl ether (VI), reaction with 4-cyanobenzenesulfonyl chloride (VII) in the presence of pyridine provided the resine-bound sulfonamide (VIII). Addition of hydroxylamine to the cyano group of (VIII) afforded the corresponding amidoxime (IX). The required oxadiazole (XI) was obtained by acylation of (IX) with 4-(trifluoromethoxy)phenylacetic acid (X) in the presence of EDC, followed by heating in diglyme to effect the cyclization. Cleavage from the resin and simultaneous desilylation was achieved by treatment with trifluoroacetic acid in dichloromethane.