Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II). The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O. Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N. Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII). Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII). Finally, catalytic hydrogenation with Pd/C furnished JTP-20993. The title compound (JTT-501) is obtained by reaction of JTP-20993 with NH2OH.

Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II). The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O. Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N. Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII). Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII). Finally, catalytic hydrogenation with Pd/C furnished JTP-20993. The title compound (JTT-501) is obtained by reaction of JTP-20993 with NH2OH.

Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II). The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O. Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N. Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII). Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII). Finally, catalytic hydrogenation with Pd/C furnished the title compound.