1496552-50-1

Basic information

• Product Name: SofosBuvir impurity 21
• Synonyms: SofosBuvir impurity 21;Chloro (R)-Phosphoryl Sofosbuvir
• CAS NO: 1496552-50-1
• Molecular Formula: C22H29ClN3O9P
• Molecular Weight: 545.91
• Mol File: 1496552-50-1.mol
• Article Data: 9

Chemical Properties

• Appearance: /
• CAS DataBase Reference: SofosBuvir impurity 21(CAS DataBase Reference)
• NIST Chemistry Reference: SofosBuvir impurity 21(1496552-50-1)
• EPA Substance Registry System: SofosBuvir impurity 21(1496552-50-1)

Safety Data

• Hazardous Substances Data: 1496552-50-1(Hazardous Substances Data)

Usage

Description

SofosBuvir impurity 21 is a chemical compound related to Sofosbuvir, which is an antiviral medication used for the treatment of hepatitis C virus (HCV) infection. It is an impurity found in the synthesis process of SofosBuvir and may have potential applications in various industries due to its chemical properties.

Uses

Used in Pharmaceutical Industry:
SofosBuvir impurity 21 is used as a starting material for the synthesis of nucleoside phosphoramidate compounds and 2''-chloro nucleotide analogs. These compounds have potential applications in the treatment of hepatitis C virus (HCV) infection, as they can be further developed into effective antiviral drugs.
Used in Chemical Research:
SofosBuvir impurity 21 can be utilized as a research compound for studying the chemical properties and reactions of Sofosbuvir and its related compounds. This can contribute to the development of new drugs and therapies for various diseases, including hepatitis C.
Used in Quality Control:
SofosBuvir impurity 21 can be used in the quality control process of Sofosbuvir manufacturing. By analyzing and monitoring the presence of this impurity, manufacturers can ensure the purity and safety of the final product, which is crucial for the effectiveness and safety of the medication.
Used in Environmental Applications:
SofosBuvir impurity 21 may have potential applications in environmental science, such as in the development of new methods for the detection and removal of pollutants or contaminants. Its chemical properties could be harnessed to create innovative solutions for environmental challenges.

Upstream product

• 1256490-48-8 (S)-2-[(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 
• 1496551-72-4 1-((2R,3R,4R,5R)-3-chloro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 1496551-70-2 2'-deoxy-2'-chloro-2'-C-methyl-3',5'-di-O-benzoyl-N⁴-benzoylcytidine 
• 1496551-71-3 C₂₄H₂₁ClN₂O₇ 
• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 879551-01-6 (4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-meth-yl-1,3,2-dioxathiolane-4-carboxylate 2,2-dioxide 
• 1627824-09-2 (R)-2-((R)-(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphorylamino)propionic acid isopropyl ester 
• 108-21-4 Isopropyl acetate 
• 31448-54-1 2'-C-methyluridine 
• 944476-40-8 (2R,3R,3aS,9aR)-3-hydroxy-2-(hydroxymethyl)-3a-methyl-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-6-one 
• 1627824-09-2 isopropyl (2R)-2-[[(2,3,4,5,6-pentafluorophenoxy)-phenoxy-phosphoryl]amino]propanoate 
• 83159-91-5 3,5-di-O-(tert-butyldimethylsilyl)-2-deoxy-D-ribono-1,4-lactone 
• 926309-10-6 isopropyl (2R)-2-((chloro(phenoxy)phosphoryl)amino)propanoate 

Relevant articles and documents

Development and Implementation of an Aluminum-Promoted Phosphorylation in the Uprifosbuvir Manufacturing Route

A novel application of the synthesis of pronucleotide (ProTide) 5′-phosphoramidate monoesters promoted by aluminum-based Lewis acids is described. In the multikilogram synthesis of uprifosbuvir (MK-3682, 1), a clinical candidate for the treatment of hepatitis C, this methodology provided >100:1 diastereoselectivity at the phosphorus stereocenter and >100:1 selectivity for the 5′-mono phosphorylation over undesired bisphosphorylation side products. The high diastereoselectivity and mono/bis ratio achieved enabled elimination of the tedious workup associated with the tert-butyl magnesium chloride protocol commonly used to install this functionality in similar nucleotide prodrugs, achieving a near doubling of the isolated yield from 45% to 81%. The process development and purity control strategy of MK-3682, as well as handling of the pyrophoric reagent on scale, will also be discussed.

Synthesis and Anti-HCV Activities of 4′-Fluoro-2′-Substituted Uridine Triphosphates and Nucleotide Prodrugs: Discovery of 4′-Fluoro-2′- C-methyluridine 5′-Phosphoramidate Prodrug (AL-335) for the Treatment of Hepatitis C Infection

We report the synthesis and biological evaluation of a series of 4′-fluoro-2′-C-substituted uridines. Triphosphates of the uridine analogues exhibited a potent inhibition of hepatitis C virus (HCV) NS5B polymerase with IC50 values as low as 27 nM. In an HCV subgenomic replicon assay, the phosphoramidate prodrugs of these uridine analogues demonstrated a very potent activity with EC50 values as low as 20 nM. A lead compound AL-335 (53) demonstrated high levels of the nucleoside triphosphate in vitro in primary human hepatocytes and Huh-7 cells as well as in dog liver following a single oral dose. Compound 53 was selected for the clinical development where it showed promising results in phase 1 and 2 trials.

A multifunctional catalyst that stereoselectively assembles prodrugs

The catalytic stereoselective synthesis of compounds with chiral phosphorus centers remains an unsolved problem. State-of-the-art methods rely on resolution or stoichiometric chiral auxiliaries. Phosphoramidate prodrugs are a critical component of pronucleotide (ProTide) therapies used in the treatment of viral disease and cancer. Here we describe the development of a catalytic stereoselective method for the installation of phosphorusstereogenic phosphoramidates to nucleosides through a dynamic stereoselective process. Detailed mechanistic studies and computational modeling led to the rational design of a multifunctional catalyst that enables stereoselectivity as high as 99:1.