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

• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 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

• 1190307-88-0 sofosbuvir 
• 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 

Relevant articles and documents

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.

Preparation method of sofosbuvir products in crystal and amorphous forms

The invention discloses a preparation method of sofosbuvir products in crystal and amorphous forms. The preparation method comprises the following steps: (1) preparation of sofebuvir: (2'R)-2'-deoxy-2'-fluorine-2'-methyluridine and N-[(S)-(2, 3, 4, 5, 6-pentafluorophenoxy) phenoxyphosphatidyl]-L-alanine isopropyl ester are used for preparing the crude product of sofebuvir under the action of a grignard reagent under anhydrous and anaerobic conditions; (2) preparation of sofosbuvir product in crystal form: the crude product of sofebuvir is placed in a ketones solvent, a decolorant is added, andthe sofosbuvir product in crystal form is obtained after dissolution, decolorization, crystallization and dryness; and (3) preparation of sofosbuvir product in amorphous form: the crude product of sofebuvir is placed in the ketones solvent, the decolorant is added, and the sofosbuvir product in amorphous form is obtained after dissolution, decolorization, crystallization, pulverization and dryness. The preparation method has the advantages of being simple and practicable, strong in operability, less in waste generation and lower in cost, and effectively solves deficiencies existing in the existing preparation method for the sofosbuvir product in crystal form.

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).