Off-White Low Melting Solid
Ixoten,Asta,W. Germany,1973
Antineoplastic; one derivative
ChEBI: Trofosfamide is a member of ifosfamides.
259 g (1 mol) of N,N-bis-(2-chloroethyl)-phosphoric acid amide dichloride,
209 g (1.2 mols) of N-(2-chloroethyl)-N-(3-hydroxypropyl)-amine
hydrochloride (crude), 1,000 cc of ethylene dichloride and 344 g (3.4 mols) of
triethylamine are the reactants. N,N-bis-(2-chloroethyl)-phosphoric acid amide
dichloride is dissolved in the methylene dichloride. N-(2-chloroethyl)-N-(3-
hydroxypropyl)-amine hydrochloride is suspended in this solution and
triethylamine is added thereto dropwise with stirring. The temperature of the
solution rises to boiling, After the termination of the addition, the mixture is
heated to boiling for another 6 hours. Thereafter, the reaction mixture is
cooled down and allowed to stand overnight at about 0°C. The precipitated
triethylamine hydrochloride is filtered off with suction. The resulting solution is
evaporated, the residue (about 370 g) is triturated with about 3.2 liters of
ether and is heated to boiling for a short period of time.
The ethereal solution is decanted from the insolubles (about 90 g). The
solution is rendered to pH 6.5 to 7 by the addition of ethereal hydrochloric
acid and then is filtered over charcoal and thereafter is evaporated. During
evaporation, the temperature should not rise above 40°C. The residue is
dissolved in ether and in an amount corresponding to half of its weight (240 g
of residue, dissolved in 120 cc of ether), the ethereal solution is cooled to -
5°C and is inoculated. After standing for 25 hours, 140 g have been separated
by crystallization. After separation by filtration with suction, the mother liquor
is diluted with ether to 5 times its volume, the solution is filtered over
charcoal, is again evaporated and the residue is again dissolved in a volume
corresponding to half of the weight of the residue. Another cooling to -5°C
and inoculation produces further 18 g of the desired compound. MP: 50° to
51°C. Total yield: 161 g (50% of the theoretical)
Poison by
intraperitoneal, subcutaneous, and
intravenous routes. Moderately toxic by
ingestion. Human mutation data reported.
Human systemic effects by unspecified
routes: hematuria, leukopenia, and
thrombocytopenia. When heated to
decomposition it emits very toxic fumes of
Cl-, NOx, and POx.
