TUMOUR CHEMOTHERAPY——XVI. SYNTHESIS OF γ-p-BIS-(2-CHLOROETHYL)-AMINOMETHYL-PHENYL-BUTYRIC ACID AND4-p-BIS-(2-CHLOROETHYL)-AMINOMETHYL-PHENYL-BUTANOL

The synthesis of γ-p-bis-(2-chloroethyl)-aminomethyl-phenyl-butyric acid hydrochloride (Ⅳ) as well as its methyl ester (Ⅺ) and ethyl ester (Ⅻ) from p-chloromethylphenylbutyric acid (Ⅵ) was described. Compound Ⅵ was first converted to methyl ester (Ⅶ) and ethyl ester (Ⅷ) and then condensed with diethanolamine, forming the corresponding bis-(2-hydroxyethyl)-amino derivatives (Ⅸ and Ⅹ). Compound Ⅸ(or Ⅹ) was chlorinated by treatment with thionyl chloride to give Ⅺ (or Ⅻ), which was subjected to hydrolysis in boiling hydrochloric acid to yield Ⅳ. Reduction of ethyl γ-p-bis-(2chloroethyl)-aminomethyl-phenyl-butyrate (Ⅻ) by lithium aluminium hydride gave the expected compound Ⅴ. Preliminary pharmacological tests revealed that these compounds did not have any siginificant inhibitory activity against sarcoma 180 in mice.