1190308-01-0

Basic information

• Product Name: PSI-7976
• Synonyms: PSI-7976;N-[[P(R),2'R]-2'-Deoxy-2'-fluoro-2'-methyl-P-phenyl-5'-uridylyl]-L-alanine 1-methylethyl ester;Sofosbuvir Impurity 19;Sofosbuvir (R)-Phosphate;(S)-isopropyl 2-((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate;isopropyl ((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-Lalaninate
• CAS NO: 1190308-01-0
• Molecular Formula: C₂₂H₂₉FN₃O₉P
• Molecular Weight: 529.4525242
• Mol File: 1190308-01-0.mol

Chemical Properties

• Appearance: /
• Density: 1.41±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), DMSO (Slightly), Ethyl Aceatae (Slightly)
• PKA: 9.39±0.10(Predicted)
• CAS DataBase Reference: PSI-7976(CAS DataBase Reference)
• NIST Chemistry Reference: PSI-7976(1190308-01-0)
• EPA Substance Registry System: PSI-7976(1190308-01-0)

Safety Data

• Hazardous Substances Data: 1190308-01-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PSI-7976 is used as an antiviral agent for the treatment of hepatitis C. It is currently being investigated in phase 3 clinical trials and has shown selective inhibitory effects towards HCV NS5B polymerase, making it a promising candidate for the treatment of hepatitis C.

Upstream product

• 1334513-02-8 (S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester 
• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 770-12-7 O-phenyl phosphorodichloridate 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 1337529-56-2 (S)-2-[(S)-(2,3,4,5,6-pentafluoro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 
• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 108-95-2 phenol 
• 793-10-2 p-nitrophenyl phenyl phosphorochloridate 
• 1256490-48-8 (S)-2-[(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 
• 1256490-49-9 (S)-2-[(R)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 
• 1256490-31-9 (S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester 

Relevant articles and documents

Method for preparing sofosbuvir

The invention discloses a method for preparing sofosbuvir. The method comprises the following steps: reacting tetrahydrofuran with a tetrahydrofuran solution of a material A, a material B, DMAP and ananiline compound under the protection of nitrogen, and monitoring the reaction by TLC until the reaction of the material A is finished, wherein the aniline compound is N,N-dimethylaniline or N,N-diethylaniline; and carrying out post-treatment on the obtained reaction product. The method for preparing sofosbuvir has the advantages of high reaction efficiency, high product yield (up to 90% or above), high purity (up to 98% or above), easiness in industrial large-scale production and great application values.

Preparation method of anti-hepatitis C medicine sofosbuvir

The invention discloses a preparation method of an anti-hepatitis C medicine sofosbuvir. The method comprises the following steps: taking r-ethyl glycerate acetonide as an initial raw material, enabling the r-ethyl glycerate acetonide to react with ethyl alpha-fluoropropionate under the action of potassium tert-butoxide, performing carbonyl reduction, hydroxyl acylation, hydrolytic cyclization under an acidic condition, hydroxyl acylation, red aluminum reduction and chiral column separation so as to obtain a sofosbuvir key intermediate ((2R,3R,4R,5R)-3-(benzoyloxy)-5-hydroxy-4-fluoro-4-methyltetrahydrofuran-2-yl) methyl benzoate, performing 2-hydroxyl acetylation, enabling acetylized material to react with 2-trimethylsiloxy-4-benzamidopyrimidine, removing benzamido under an acidic condition, performing dehydroxylation protection, and finally enabling obtained material to react with N-[(S)-(2,3,4,5,6-Pentafluorophenoxy)phenoxyphosphinyl]-L-alanine 1-methylethyl ester to obtain the sofosbuvir. The method has the advantages of short synthesis route, high yield, avoidance of a fluorination reaction step in the synthesis process, and mild synthesis reaction conditions.

Novel process for preparing sofosbuvir

The invention provides a preparation process for sofosbuvir. According to the invention, in a butting process of two key fragments, tert-butylmagnesium chloride/lithium chloride is used as base, so selectivity of the base is improved; the conversion rate

PROCESS FOR THE PREPARATION OF (Sp)-SOFOSBUVIR AND INTERMEDIATES THEREOF

The present invention is directed towards process for preparation of an optically pure (Sp)-Sofosbuvir of Formula-(I) and its intermediate namely (Sp)-isomer of isopropyl alanyl phosphoramidate of Formula (III) thereof.

Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.

SELECTIVE PROCESS FOR SYNTHESIS OF NUCLEOSIDE PHOSPHORAMIDATES

A process for preparing a nucleoside phosphoramidate, in particular to a process for preparing sofosbuvir, wherein a phosphoramidate derivative is used as starting material.

NUCLEOSIDE PHOSPHORAMIDATES USEFUL FOR THE TREATMENT OF VIRAL INFECTIONS AND PREPARATION THEREOF

The present invention relates to an industrially applicable process for the preparation of phosphoramidates useful for the treatment of viral infections, such as sofosbuvir, and to intermediates useful for the preparation thereof. Formula (I):

USE OF A L,3J5-TRIAZIN-2-YL PHOSPHORAMIDATE COMPOUND IN THE SYNTHESIS OF SOFOSBUVIR

The present invention relates to a new type of 1,3.5-triazin-2-yl phosphoramidates of general formula I with the absolute configuration (S) at the phosphorus atom, an Sp diastereoisomer, wherein R1 and R2 can independently be H, a C1-C6 (un)branched alkyl, a C1-C6 (un)branched alkoxy group, a C1-C6 (un)branched alkylsulfanyl group, C1-C6 (un)branched monoalkylamino or dialkylamino group, including cyclic amino groups, e.g. pyrrolidino, piperidino or morpholino group; and to their use for the production of biologically active phosphoramidate prodrugs, especially sofosbuvir of formula II. Sofosbuvir II is a nucleotide inhibitor of the RNA polymerase, used for the treatment of hepatitis C in the form of a prodrug, releasing the active antiviral agent 2'-deoxy-2'-a-fluoro- P-C-methyluridine-5'-triphosphate in the organism.

METHODS OF STEREOSELECTIVE SYNTHESIS OF SUBSTITUTED NUCLEOSIDE ANALOGS

The present invention relates to the novel diastereoselective syntheses for generating phosphorothioate compounds. Examples include nucleoside phosphorothioate analogs that are useful in treating diseases and/or conditions such as viral infections.

Synthesis of diastereomerically pure nucleotide phosphoramidates

Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5′-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.