合成路线1

(S)-Piperazine-2-carboxylic acid (I) was sequentially protected as the 4-Boc derivative (II) and then as the 1-Alloc-4-Boc-piperazine (III). After conversion of (III) to benzyl ester (IV), its N-Boc group was selectively removed by treatment with trifluoroacetic acid. The resultant 4-deprotected piperazine (V) was then alkylated with 3-chloro-3-methyl-1-butyne (VI) yielding (VII). Copper-promoted coupling of 4-hydroxy-3,5-diiodopyridine (IX) prepared by halogenation of 4-hydroxypyridine (VIII) with N-iodosuccinimide with the propargyl piperazine (VII) gave rise to the furo[3,2-c]pyridine derivative (X). The N-Alloc protecting group was then replaced by the N-Boc group to yield (XII) via palladium catalyzed deprotection of (X), followed by treatment of the resultant piperazine (XI) with Boc2O. Simultaneous hydrogenolysis of the benzyl ester and the iodo substituent of (XII) led to acid (XIII). After coupling of (XIII) with 2,2,2-trifluoroethylamine, acidic cleavage of the N-Boc group furnished the piperazine-2-carboxamide (XIV).