I. Neda et al., A NEW METHOD FOR THE PREPARATION OF IFOSFAMIDE AND CYCLOPHOSPHAMIDE, Zeitschrift fur Naturforschung. B, A journal of chemical sciences, 52(8), 1997, pp. 943-946
The reaction of ethyl)-tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide 1 a
nd chloro-tetrahydro-2H-1,3,2-oxazaphosphorin-2-oxide 2 with 2-(trimet
hylsilyloxy)ethylamine 3 and bis-[2-(trimethylsiloxy)ethyl]amine 4, re
spectively, yielded the trimethylsilylated compounds 5 and 6, analogou
s to ifosfamide and cyclophosphamide. The reaction of 5 and 6 with ,3,
5-trimethyl-1,3,5-triaza-2-phosphorin-4,6-dione 7 led to the diphospho
rus compounds 8 and 9 which could be transformed to ifosfamide 11 and
cyclophosphamide 12 by treatment with sulfuryl chloride. This synthesi
s shows that the alkylating agents 2-chloroethylammonium chloride and
bis-(2-chloroethyl)ammonium chloride can be avoided and the chlorine a
tom can be introduced in the final reaction step of the synthesis of 1
1 and 12.