1064684-44-1

Basic information

• Product Name: Sofosbuvir
• Synonyms: PSI 7977; L-Alanine, N-[[p(S),2'R]-2'-deoxy-2'-fluoro-2'-methyl-p-phenyl-5'-uridylyl]-, 1-methylethyl ester; Psi-7977; (S)-isopropyl 2-(((S)-(((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)amino)propanoate; sofosvuvir form6; sovaldi API; sofosbuvir form6; GS-7977; Sopropyl-(2S)-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl]-4-fluoro-3-hydroxy-4-methy-ltetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate; Sofasbuvir
• CAS NO: 1064684-44-1
• Molecular Formula: C₂₂H₂₉FN₃O₉P
• Molecular Weight: 529.45
• Mol File: 1064684-44-1.mol
• Article Data: 17

Chemical Properties

• CAS DataBase Reference: Sofosbuvir(CAS DataBase Reference)
• NIST Chemistry Reference: Sofosbuvir(1064684-44-1)
• EPA Substance Registry System: Sofosbuvir(1064684-44-1)

Safety Data

• Hazardous Substances Data: 1064684-44-1(Hazardous Substances Data)

Usage

General Description

Sofosbuvir is an antiviral medication used to treat chronic hepatitis C (Hep C). It inhibits the Hep C virus's specific enzyme, known as NS5B RNA-dependent RNA polymerase, and is incorporated into HCV's RNA by the NS5B protein, resulting in viral chain termination. It's an effective treatment alone or in combination with other drugs, reducing significant complications of Hep C, such as cirrhosis and liver cancer. While generally well-tolerated, common side effects include fatigue, headache, nausea, and difficulty sleeping. It is taken orally and is marketed under the brand name Sovaldi, among others.

Upstream product

• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 1256490-52-4 (S)-2-[(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphorylamino]propionic acid isopropyl ester 
• 770-12-7 O-phenyl phosphorodichloridate 
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• 879551-04-9 (3R,4R,5R)-3?fluoro?4?hydroxy?5?(hydroxymethyl)?3?methyltetrahydrofuran?2?one 
• 1160557-97-0 1-((2R,3R,4R,5R)-5-((tert-butyldimethylsilyloxy)methyl)-3-fluoro-4-hydroxy-3-methyl-tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione 
• 874638-98-9 N-(1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)benzamide 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 1500076-79-8 (2R)-2-deoxy-2-fluoro-2-methyl-α/β-D-erythro-pentofuranosyl chloride-3,5-dibenzoate 

Downstream Products

• 1233335-78-8 (2S)-2-((((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoic acid 
• 1190307-88-0 sofosbuvir 

Relevant articles and documents

Sofosbuvir synthesis process

The invention relates to a sofosbuvir synthesis process. A traditional sofosbuvir synthesis process is optimized and improved, 1-((2R,3R,4R,5R)-3-fluro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione and isopropyl(S)-(perfluorophenoxyl)(phenoxy)phospho)-L-alanine are taken as raw materials, tert-butylmagnesium chloride is added in batches to obtain a reactant,the reactant is quenched through ethyl acetate hydrochloride and subjected to decompression concentration, then dissolving is conducted through ethyl acetate, washing is conducted through hydrochloricacid, the pH of a reaction system is adjusted through sodium bicarbonate, then decompression distillation and methyl tertiary ether are conducted, silica gel is used for adsorption, then dichloromethane is used for crystallization, then filtering, washing and drying are conducted, and thus white powder sofosbuvir is obtained. The sofosbuvir synthesis process has the advantages of cost lowering, energy saving and environmental protection, and the yield of the obtained sofosbuvir reaches up to 90%.

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.

PROCESS FOR THE PREPARATION OF SOFOSBUVIR

The present invention relates to a process for the synthesis of Sofosbuvir of formula (I) comprising the selective mono-deacetylation reaction of a compound of formula (V) to obtain a compound of formula (IV).