82475-49-8

Upstream product

• 127-88-8 N,N-di(2-chloroethyl)amidophosphoric acid dichloride 
• 865-34-9 lithium methanolate 
• 67-56-1 methanol 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 2524-03-0 dimethyl chlorothiophosphate 

Downstream Products

• 82475-53-4 O,O-bis(tert-butyldiphenylsilyl)-N,N-bis(2-chloroethyl)phosphoramidate 
• 82475-51-2 O,O-bis(tert-butyldimethylsilyl)-N,N-bis(2-chloroethyl)phosphoramidate 
• 82475-52-3 O,O-bis(diphenylmethylsilyl)-N,N-bis(2-chloroethyl)phosphoramidate 

Relevant academic research and scientific papers

Decomposition of N-Phosphorylated Nitrogen Mustards: A Mechanistic Investigation

Lithium methyl N-(2-chloroethyl)phosphoramidate (2b) and lithium methyl N,N-bis(2-chloroethyl)phosphoramidate (2c) were prepared as models of N-phosphorylated mustards used in cancer chemotherapy.The decomposition of those substrates in D2O and in D2O-pyridine-d5 was studied to elucidate the mechanism of their alkylating reactivity.The products of the decomposition and the variation of the proportions of the products with time were determined, and the results led to the following conclusions.Decomposition of substrates of the type 2 can follow three independent pathways: (i) 1,5-cyclization to a 1,3,2-oxazaphospholidine derivative, followed by fast ring opening via the pH-dependent P-O or P-N bond cleavage; (ii) 1,3-cyclization to a N-phosphorylated aziridinium derivative, followed by the nucleophilic opening of the aziridine ring; (iii) fragmentation to metaphosphate and aziridine species, followed by rapid reactions of those intermediates with nucleophiles.The first pathway deactivates the substrate with respect to the alkylating reactivity.Relative contributions of individual pathways to the decomposition are highly sensitive to the detailed structure of the substrate and to the nucleophilic composition of the reaction medium.

DERIVES THIOPHOSPHORYLES DE LA BIS(2-CHLOROETHYL)AMINE PREPARATION D'ALKOXY-2 OXO-2 CHLOROETHYL-3 THIAZAPHOSPHOLIDINE-1,3,2

The reaction of bis(chloroethyl-2)amine with dimethylthiochlorophosphate in anhydrous methylene chloride proceeds by an initial quantitative P-N bond formation rapidly followed by a spontaneous exothermic intramolecular cyclisation to a thiazaphospholidine ring.Using higher alkyl thiochlorophosphates as starting materials the thiophosphoramidates were first obtained; cyclisation is done either by pyrolysis or by heating in CH3CN.All the thiazaphospholidine rings undergo cleavage of the P-N bond in aqueous acetone.Direct 31P NMR monitoring of the formation of thiazaphospholidines reveals unambiguously the intervention of a phosphonium P(IV)+ intermediate which suggest that the reaction mechanism is of the Michaelis-Arbuzov type.

Synthesis, hydrolytic reactivity, and anticancer evaluation of N-and O-triorganosilylated compounds as new types of potential prodrugs

N- and O-Triorganosilylated compounds related to various anticancer agents were synthesized for evaluation as potential anticancer prodrugs. 1H-NMR and UV kinetic measurements of hydrolytic desilylation were used to correlate relative rates of structural unmasking with steric bulk about the silicon reaction center. The tert-butyldimethylsilyl ester of chlorambucil and a number of O-triorganosilylated carbamate derivatives of nor-nitrogen mustard showed significant activity against P-388 lymphocytic leukemia in mice.