Analysis of ifosfamide, 4-hydroxyifosfamide, N2-dechloroethylifosfamide, N3-dechloroethylifosfamide and iphosphoramide mustard in plasma by gas chromatography-mass spectrometry

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

“…Relative to LiAlH 4 , AlH 3 is a better Lewis acid and reacts quickly with nitriles under mild conditions 16 ; thus, AlD 3 was used to reduce nitriles in this work. Products were obtained in nearly quantitative yield and were of much higher purity than those generated from LiAlD 4 . The higher quality of these difficult-to-purify amines led to improved yields when they were incorporated into subsequent reactions.…”

“…6 ! 5, $90%), LiAlH(D) 4 reactions with nitriles have given products that were low in yield and difficult to purify. Relative to LiAlH 4 , AlH 3 is a better Lewis acid and reacts quickly with nitriles under mild conditions 16 ; thus, AlD 3 was used to reduce nitriles in this work.…”

“…The higher quality of these difficult-to-purify amines led to improved yields when they were incorporated into subsequent reactions. For example, in the synthesis of [4, H 2 ]-(1), use of deuterated 4 generated by LiAlD 4 gave a net yield of $20%…”

“…[1][2][3][4] Competing with this reaction in 1 and 2 are oxidations at the a and a 0 positions, each of which leads to a dechloroethylation and the formation of the neurotoxic chloroacetaldehyde. Dechloroethylation is a minor ($10%) pathway in the metabolism of 1 3,5 but can constitute up to 50% of the metabolism of 2.…”

“…Dechloroethylation is a minor ($10%) pathway in the metabolism of 1 3,5 but can constitute up to 50% of the metabolism of 2. 3,4 For MS studies of the enzymatic, kinetic, mechanistic, and stereochemical factors that influence the oxidation of 1 and 2 at one site relative to another, the following were synthesized: [4, …”