Coupling of tyramine (I) with p-nitrophenyl isocyanate (II) affords urea (III). Subsequent nitro group reduction with H2 and Pd/C gives amine (IV). Condensation of amine (IV) with ethylene oxide (V) leads to the bis-hydroxyethyl amine (VI). This is finally chlorinated employing SOCl2 in pyridine. Alternatively, amine (IV) is subjected to reductive alkylation with chloroacetaldehyde and NaBH3CN to furnish the target bis-chloroethyl amine. (1,2)
In an alternative method, p-nitroaniline (I) is reacted with ethylene oxide (II) to afford diol (III). This compound can also be prepared by condensation of 1-fluoro-4-nitrobenzene (IV) with diethanolamine (V). Chlorination of diol (III) to provide (VI) is accomplished with either mesyl chloride or SOCl2 in the presence of pyridine. Then, nitro group reduction in (VI) by means of iron and HCl affords aniline (VII).
Reaction of tyramine (VIII) with p-nitrophenyl chloroformate (IX) gives rise to the nitrophenyl carbamate (X). Finally, coupling of (X) with aniline (VII) provides the title urea.