Em. Shulmanroskes et al., SYNTHESIS OF N-15 LABELED ISOPHOSPHORAMIDE MUSTARD, Journal of labelled compounds & radiopharmaceuticals, 34(3), 1994, pp. 231-237
The ifosfamide metabolite isophosphoramide mustard (IPM) was synthesiz
ed with isotopic enrichment at each nitrogen site. Glycine-N-15 was co
nverted to 2-chloroethylamine-N-15 hydrochloride (4 steps, 21% net yie
ld) which was then reacted with phenyl dichlorophosphate to provide N,
N'-bis(2-chloroethyl)phosphorodiamidic-N-15(2) acid phenyl ester [62%,
PhOP(O) ((NHCH2CH2Cl)2)-N-15]. Catalytic hydrogenation of this phenyl
ester followed by the addition of cyclohexylamine (CHA) provided IPM-
N-15(2) as the CHA salt (63%).