116384-53-3

Basic information

• Product Name: [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester
• Synonyms: 9-[2-(DIETHYLPHOSPHONOMETHOXY)ETHYL]ADENINE;[[2-(6-AMINO-9H-PURIN-9-YL)ETHOXY]METHYL]PHOSPHONIC ACID DIETHYL ESTER;9-[2-(Diethylphosphonomethoxy)ethyl]adenine（Diethyl PMEA）;9-[2-(6-amino-9H-purin-9-yl)ethoxy]methyl]phosphonicaciddiethylester;[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester(A3);Adefovir Dipivoxil InterMediates;Diethyl [[2-(6-AMino-9H-purin-9-yl)ethoxy]Methyl]phosphonate;Diethyl [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonate
• CAS NO: 116384-53-3
• Molecular Formula: C₁₂H₂₀N₅O₄P
• Molecular Weight: 329.29
• EINECS: 1806241-263-5
• Mol File: 116384-53-3.mol

Chemical Properties

• Melting Point: 134.0 to 138.0 °C
• Boiling Point: 531.1 ºC at 760 mmHg
• Flash Point: 275 ºC
• Appearance: light yellow liquid
• Density: 1.45 g/cm³
• Vapor Pressure: 2.32E-11mmHg at 25°C
• Refractive Index: 1.619
• PKA: 4.18±0.10(Predicted)
• CAS DataBase Reference: [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester(116384-53-3)
• EPA Substance Registry System: [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester(116384-53-3)

Safety Data

• Hazardous Substances Data: 116384-53-3(Hazardous Substances Data)

Usage

Uses

Given the lack of explicit information on the specific uses of [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester, potential applications can be hypothesized based on its structural components and typical roles of similar compounds in various industries:
Used in Pharmaceutical Industry:
[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester could be used as a bioactive compound for the development of new drugs, given its purine and phosphonic acid components, which are often found in biologically active molecules. Its potential role in enzyme catalysis and substrate binding may contribute to its efficacy in treating specific diseases or conditions.
Used in Chemical Research:
In the field of chemical research, [[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester may serve as a subject for studying the synthesis and properties of complex organic compounds, as well as exploring its reactivity and potential interactions with other molecules.
Used in Material Science:
[[2-(6-Amino-9H-purin-9-yl)ethoxy]methyl]phosphonic acid diethyl ester might also be utilized in material science for the development of new materials with specific properties, such as catalytic activity or binding capabilities, based on its ester formation and the presence of purine and ethoxy groups.

InChI:InChI=1/C12H20N5O4P/c1-3-20-22(18,21-4-2)9-19-6-5-17-8-16-10-11(13)14-7-15-12(10)17/h7-8H,3-6,9H2,1-2H3,(H2,13,14,15)

Upstream product

• 116384-56-6 2-chloroethoxymethyl phosphonic acid diethyl ester 
• 66224-66-6 adenine 
• 116384-57-7 Diethyl 2-Bromoethoxymethanephosphonate 
• 116384-58-8 toluene-4-sulfonic acid 2-(diethoxy-phosphorylmethoxy)-ethylester 
• 64-17-5 ethanol 
• 142341-38-6 C₈H₁₀Cl₂N₅O₂P 
• 31618-90-3 diethyl (p-toluenesulfonyloxymethane)phosphonate 
• 707-99-3 9-(2-hydroxyethyl)adenine 
• 3084-40-0 diethyl (1-hydroxymethyl)phosphonate 
• 100708-15-4 2-((diethoxyphosphoryl)methoxy)ethyl acetate 
• 116384-55-5 diethyl 2-hydroxyethoxymethanephosphonate 
• 591251-47-7 N₉-(2-iodoethyl)adenine 
• 106938-62-9 (diethoxyphosphinyl)methyl trifluoromethanesulfonate 
• 1670-62-8 6-Chloro-9-(β-hydroxyethylamino)purine 

Downstream Products

• 106941-25-7 Adefovir 
• 116384-54-4 Ethyl Ester of 9-(2-Phosphonylmethoxyethyl)adenine 
• 153235-85-9 N⁶-4-monomethoxytrityl-9-[2-(diethylphosphonylmethoxy)ethyl]adenine 
• 872191-06-5 N⁶-4-monomethoxytrityl-9-[2-(cycloSal-phosphonylmethoxy)ethyl]adenine 
• 872191-08-7 N⁶-4-monomethoxytrityl-9-{2-[(3-methyl-cycloSal)phosphonylmethoxy]ethyl}adenine 
• 872191-10-1 N⁶-4-monomethoxytrityl-9-{2-[(3-tert-butyl-cycloSal)phosphonylmethoxy]ethyl}adenine 
• 872191-12-3 N⁶-4-monomethoxytrityl-9-{2-[(3,5-di-tert-butyl-cycloSal)phosphonylmethoxy]ethyl}adenine 
• 142341-04-6 9-<2-(phosphonomethoxy)ethyl>adenine, monoethyl mono(pivaloyloxy)methyl ester 
• 142340-99-6 adefovir dipivoxyl 

Relevant articles and documents

Ester prodrugs of acyclic nucleoside thiophosphonates compared to phosphonates: Synthesis, antiviral activity and decomposition study

9-[2-(Thiophosphonomethoxy)ethyl]adenine [S-PMEA, 8] and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine [S-PMPA, 9] are acyclic nucleoside thiophosphonates we described recently that display the same antiviral spectrum (DNA viruses) as approved and potent phosphonates PMEA and (R)-PMPA. Here, we describe the synthesis, antiviral activities in infected cell cultures and decomposition study of bis(pivaloyloxymethoxy)-S-PMEA [Bis-POM-S-PMEA, 13] and bis(isopropyloxymethylcarbonyl)-S-PMPA [Bis-POC-S-PMPA, 14] as orally bioavailable prodrugs of the S-PMEA 8 and S-PMPA 9, in comparison to the equivalent "non-thio" derivatives [Bis-POM-PMEA, 11] and [Bis-POC-PMPA, 12]. Compounds 11, 12, 13 and 14 were evaluated for their in vitro antiviral activity against HIV-1-, HIV-2-, HBV- and a broad panel of DNA viruses, and found to exhibit moderate to potent antiviral activity. In order to determine the decomposition pathway of the prodrugs 11, 12, 13 and 14 into parent compounds PMEA, PMPA, 8 and 9, kinetic data and decomposition pathways in several media are presented. As expected, bis-POM-S-PMEA 13 and bis-POC-S-PMPA 14 behaved as prodrugs of S-PMEA 8 and S-PMPA 9. However, thiophosphonates 8 and 9 were released very smoothly in cell extracts, in contrast to the release of PMEA and PMPA from "non-thio" prodrugs 11 and 12.

Synthesis, in vitro antiviral evaluation, and stability studies of novel α-borano-nucleotide analogues of 9-[2-(phosphonomethoxy)ethyl]adenine and (R)-9-[2-(phosphonomethoxy)propyl]adenine

We describe here the synthesis of 9-[2-(Boranophosphonomethoxy)ethyl] adenine (6a) and (R)-9-[2-(Boranophosphonomethoxy)propyl]adenine (6b), the first α-boranophosphonate nucleosides in which a borane (BH3) group substitutes one nonbridging oxygen atom of the α-phosphonate moiety. H-phosphinates 5a and 5b and α-boranophosphonates 6a and 6b were evaluated for their in vitro activity against human immunodeficiency virus (HIV) infected cells and against a panel of DNA or RNA viruses. Compounds 5a, 5b, 6a, and 6b exhibited no significant antiviral activity in vitro and cytotoxicity. To measure the chemical and enzymatic stabilities of the target compounds 6a and 6b, kinetic data of decomposition for derivatives 5a, 5b, 6a, 6b, and standard compounds were studied at 37 °C in several media. The α- Boranophosphonates 6a and 6b were metabolized in culture medium into H-phosphinates 5a and 5b, with half-live values of 5.3 h for 6a and 1.3 h for 6b.

Process optimization in the synthesis of 9-[2-(diethylphosphonomethoxy)ethyl]adenine: replacement of sodium hydride with sodium tert-butoxide as the base for oxygen alkylation

9-[2-(Diethylphosphonomethoxy)ethyl]adenine (diethyl-PMEA), a key intermediate in the production of the antiviral drug adefovir dipivoxil, was originally produced via a process utilizing sodium hydride (NaH) to couple hydroxyethyl adenine with diethyl p-toluenesulfonyloxymethanephosphonate. The use of NaH presented safety and consistency problems. It was found that sodium tert-butoxide (NaOBu) was a suitable replacement for NaH as the base to effect the coupling reaction. Optimization of reagent stoichiometry and introduction of a simplified filtration workup procedure led to a robust process affording diethyl-PMEA in consistent yields and purities. The modifications and process improvements were scaled-up successfully to batch sizes of >100 kg.

Preparation method of nucleoside phosphate prodrug

The invention belongs to the field of pharmaceutical chemicals, and relates to a preparation method of a nucleoside phosphate prodrug. A diphenol phosphate intermediate A and an alcohol compound B are subjected to a transesterification reaction to obtain the nucleoside phosphate prodrug. According to the method, rapid synthesis of different nucleoside prodrugs is achieved through exchange of the base-catalyzed nucleoside diphenyl phosphate intermediate and alcohol, synthesis of a target compound is achieved through one-step reaction, meanwhile, use of strong acid and high-toxicity chlorides is avoided, the safety of generation can be improved, the cost is reduced, and emission of three wastes is reduced.

An improved synthesis of adefovir and related analogues

An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how regioselectivity is affected by the substitution pattern of the nucleobase. Finally, this chemistry was successfully applied to the synthesis of several new adefovir analogues, highlighting the versatility of our approach.

Synthetic method of adefovir dipivoxil

The invention relates to the field of chemical pharmaceuticals, in particular to an industrial production and synthesis process of an adefovir dipivoxil bulk drug. 9-(2-hydroxyethyl)-adenine and diethyl p-toluenesulfonyloxymethyl phosphate serve as raw materials, and under the action of a catalyst, adefovir dipivoxil is produced through esterification, desalination and hydrolysis. The adefovir dipivoxil is subjected to acid and alkali refining, then condensed with chloromethyl valerate, then separated and purified to obtain adefovir divalentyl oxymethyl ester raw materials. The synthetic process is an industrialized production process, the operation is simple, adefovir dipivoxil is suitable for large-scale production, and the production cost can be greatly reduced.

Preparation method of adefovir dipivoxil crystals

The invention belongs to the technical field of drug preparation and in particular relates to a preparation method of adefovir dipivoxil crystals. The preparation method comprises the following steps: synthesizing diethyl phosphite; synthesizing diethyl (p-phenylsulfonyloxy)methylphosphonate; synthesizing 9-(2-hydroxyethyl) adenine; synthesizing 4,9-[2-(diethylphosphonomethoxy)ethyl]adenine; synthesizing adefovir; synthesizing adefovir dipivoxil. Compared with the prior art, the preparation method of the adefovir dipivoxil crystals, provided by the invention, takes acetonitrile as a water-soluble organic medium, and the difficulty that DMF (Dimethyl Formamide) is difficult to remove is overcome; ethyl acetate is used for replacing isopropyl acetate in a previous process, isopropyl ether is used for replacing ethyl ether and ethanol is used for replacing acetone; the preparation method is simple to operate; the obtained product has good purity and high yield; the industrialized production is easy to realize and the production cost is reduced.

Adefovir dipivoxil a hydrate and its preparation method (by machine translation)

Adefovir dipivoxil this invention relates to a method for preparing a hydrate thereof, with an aqueous acetone as the solvent, can be obtained by the freeze-drying of a water composition of adefovir dipivoxil freeze-dried powder. The method is simple and convenient to operate, can selectively obtain a hydrate, high product yield, purity is good, is very suitable for large-scale production. (by machine translation)

A method for preparation of adefovir dipivoxil

The present invention discloses an adefovir dipivoxil preparation method, which comprises the following steps represented in the instruction. According to the present invention, base on the research of the existing adefovir dipivoxil synthesis route, the new synthesis route of 9-(2-hydroxyethyl)adenine is designed so as to provide the new method and the new idea for the synthesis of the drug adefovir dipivoxil, and provide help for the future drug development and production.

PROCESS FOR THE PREPARATION OF ADEFOVIR DIPIVOXIL

An improved process for the preparation of adefovir dipivoxil and its pharmaceutically acceptable salts or solvates comprises the condensation of adefovir with chloro methyl pivalate in a mixture of two or more solvents in the presence of a base and isolating the resulting adefovir dipivoxil.