A New Method of Preparation of Ifosfamide and Cyclophosphamide; Synthesis of Side Products

Abstract

This study focusses on the preparation of ifosfamide (1; R1=CH2CH2Cl, R2=NHCH2CH2Cl) and cyclophosphamide (2 R1=H, R2=N(CH2CH2Cl)2), standard drugs in tumor therapy, in order to avoid the alkylating educts like 2-chloroethylamine by introducing chlorine in the final reaction step. The reaction of the trimethylsilyl compounds (3; R1=CH2CH2Cl, R2=NHCH2CH20SiMe3) and (4; R1=H, R2=N(CH2CH20SiMe3)2), respectively, with 2-chloro- 1,3,5-trimethyl-1,3,5-triaza-σ3λ3-2-phosphoM-4,6-dione, followed by chlorination of the resulting product with sulphuryl chloride, furnished the cytotoxic drugs (1) and (2) [l].