Antineoplastic agents. XIX. N-Bis(2-haloethyl)glycine amides

Abstract

A number of routes to N-bis(2-fluoroethyl)glycine (IIIa) were explored. Of these, condensation between N-bis(2-fluoroethyl)amine and bromoacetic acid in tetrahydrofuran proved to be the most satisfactory. Reaction between a carbonic anhydride derivative of, for example, glycine IIIa and the appropriate aromatic amine provided the glycine amides summarized by structures IVb-IVi. Treatment of N-bis(2-chloroethyl)glycine hydrochloride with oxalyl chloride at steam-bath temperature yielded N-bis(2-chloroethyl)amine hydrochloride as the major product.