Labeled oxazaphosphorines for applications in MS studies. Synthesis of deuterium labeled cyclophosphamides and ifosfamides

A variety of deuterated 3‐amino‐1‐propanols were made by the LiAlD4 or AlD3 reduction of nitrile or ester precursors. The labeled aminopropanols and/or deuterated bis(2‐chloroethyl)amines were used to synthesize [4,4‐2H2]‐, [6,6‐2H2]‐, [α,α.α′,α′‐2H4]‐, and [4,4,β,β,β′,β′‐2H6]‐cyclophosphamide. The labeled aminopropanols were also used to synthesize deuterated 3‐(2′‐benzyloxyethylamino)‐1‐propanols [BnOCH2CH2NH(CH2)3OH] which, along with labeled and unlabeled 2‐chloroethylamines, led to [4,4‐2H2]‐, [6,6‐2H2]‐, [α,α‐2H2]‐, [α′,α′‐2H2]‐, [α,α.α′,α′‐2H4]‐, and [6,6,α,α,α′,α′‐2H6]‐ifosfamide. Copyright © 2007 John Wiley & Sons, Ltd. Deuterated aminopropanols, bis(2‐chloroethyl)amines and 2‐chloroethylamines were synthesized and used to generate a series of deuterated cyclophosphamides and ifosfamides. Copyright © 2007 John Wiley & Sons, Ltd.