18228-80-3

Basic information

• Product Name: benzyl N,N-bis(2-chloroethyl)phosphorodiamidate
• Synonyms: phosphorodiamidic acid, N,N-bis(2-chloroethyl)-, phenylmethyl ester
• CAS NO: 18228-80-3
• Molecular Formula: C₁₁H₁₇Cl₂N₂O₂P
• Molecular Weight: 311.1446
• Mol File: 18228-80-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 427.7°C at 760 mmHg
• Flash Point: 212.4°C
• Density: 1.318g/cm³
• Vapor Pressure: 1.61E-07mmHg at 25°C
• Refractive Index: 1.55
• CAS DataBase Reference: benzyl N,N-bis(2-chloroethyl)phosphorodiamidate(CAS DataBase Reference)
• NIST Chemistry Reference: benzyl N,N-bis(2-chloroethyl)phosphorodiamidate(18228-80-3)
• EPA Substance Registry System: benzyl N,N-bis(2-chloroethyl)phosphorodiamidate(18228-80-3)

Safety Data

• Hazardous Substances Data: 18228-80-3(Hazardous Substances Data)

Upstream product

• 100-51-6 benzyl alcohol 
• 127-88-8 N,N-di(2-chloroethyl)amidophosphoric acid dichloride 
• 20194-18-7 sodium phenyl-methanolate 
• 82576-66-7 benzyl N,N-bis(2-chloroethyl)phosphoramidochloridate 

Downstream Products

• 10159-53-2 phosphoramide mustard 

Relevant articles and documents

Design, synthesis and evaluation of targeted hypoxia-activated prodrugs applied to chondrosarcoma chemotherapy

The tumor microenvironment in chondrosarcoma (CHS), a chemo- and radio-resistant cancer provides unique hallmarks for developing a chondrosarcoma targeted drug‐delivery system. Tumor targeting could be achieved using a quaternary ammonium function (QA) as a ligand for aggrecan, the main high negative charged proteoglycan of the extracellular matrix of CHS, and a 2-nitroimidazole as trigger that enables hypoxia‐responsive drug release. In a previous work, ICF05016 was identified as efficient proteoglycan-targeting hypoxia-activated prodrug in a human extraskeletal myxoid chondrosarcoma model in mice and a first study of the structure-activity relationship of the QA function and the alkyl linker length was conducted. Here, we report the second part of the study, namely the modification of the nitro-aromatic trigger and the position of the proteoglycan-targeting ligand at the aromatic ring as well as the nature of the alkylating mustard. Synthetic approaches have been established to functionalize the 2-nitroimidazole ring at the N-1 and C-4 positions with a terminal tertiary alkyl amine, and to perform the phosphorylation step namely through the use of an amine borane complex, leading to phosphoramide and isophosphoramide mustards and also to a phosphoramide mustard bearing four 2-chloroethyl chains. In a preliminary study using a reductive chemical activation, QA-conjugates, except the 4-nitrobenzyl one, were showed to undergo efficient cleavage with release of the corresponding mustard. However N,N,N-trimethylpropylaminium tethered to the N-1 or C-4 positions of the imidazole seemed to hamper the enzymatic reduction of the prodrugs and all tested compounds featured moderate selectivity toward hypoxic cells, likely not sufficient for application as hypoxia-activated prodrugs.

Chemically Stable, Lipophilic Prodrugs of Phosphoramide Mustard as Potential Anticancer Agents

Benzyl phosphoramide mustard (3), 2,4-difluorobenzyl phosphoramide mustard (4), and methyl phosphoramide mustard (5) were examined as lipophilic, chemically stable prodrugs of phosphoramide mustard (2).These phosphorodiamidic esters are designed to underg