合成路线1

The reaction of N-(butoxycarbonyl)-3-[2-[3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetamido]-L-alanine methyl ester (I) (intermediate (VII) in scheme no. 22467601a) with hydroxylamine and TEA in hot methanol gives the N-hydroxyamidine compound (II), which is treated with Ac2O in acetic acid to yield the N-acetoxyamidino compound (III). The cyclization of (III) by means of Ac2O in refluxing acetic aid affords the 1,2,4-oxadiazole derivative (IV), which is reduced with H2 over Pd/C in methanol/HOAc to provide the amidino derivative (V). Alternatively, the direct reduction of N-acetoxyamidino derivative (III) with H2 over Pd/C in acetic acid also gives the amidino derivative (V). Finally, the methyl ester group of compound (V) is hydrolyzed with LiOH in THF to yield the target roxifiban acetate.