合成路线1

The reaction of imidazole (I) with tert-butoxycarbonyl anhydride in ethyl acetate, followed by acetylation with acetic anhydride gives the cis-ethylenediamine derivative (II), which is isomerized to its trans isomer (III) with I2 in THF. The cyclization of (III) with hydrazone (IV) by means of Na2CO3 in hot acetonitrile yields the tetrahydropyridazine (V), which s deprotected at the amino group with HCl in ethyl acetate affording the amine (VI). The condensation of (VI) with the protected thiourea (VII) by means of HgCl2 and Et3N in DMF gives the protected guanidine (VIII), which is hydrolyzed at the ester group with KOH in methanol/water providing the carboxylic acid (IX). Finally, this compound is deprotected with TFA in dichloromethane. The intermediate, the hydrazone derivative (IV) has been obtained by condensation of 2-ethylbutyryl hydrazide (X) with 3-bromo-2-oxobutyric acid ethyl ester in ethyl ether catalyzed by acetic acid.