Fischer indole cyclization of naltrexone (I) with 4-nitrophenylhydrazine (II) provided 5'-nitronaltrindole (III). Subsequent reduction of the nitro group of (III) by means of hydrazine hydrate and Raney Nickel gave the 5'-amino derivative (IV). Mercury-assisted condensation of (IV) with di(tert-butoxy-carbonyl)thiourea (V) afforded the protected guanidine (VI). Finally, the Boc groups of (VI) were cleaved by treatment with trifluoroacetic acid to furnish the title compound.

Fischer indole cyclization of naltrexone (I) with 4-(cyanomethyl)phenylhydrazine (II) produces the indolomorphinan derivative (III). Subsequent reduction of the cyano group of (III) by catalytic hydrogenation over Raney-nickel produces amine (IV). This is then condensed with methyl acetimidate (V) to furnish the corresponding amidine.