Sofosbuvir

Base Information

• Chemical Name: Sofosbuvir
• CAS No.: 1190307-88-0
• Molecular Formula: C22H29FN3O9P
• Molecular Weight: 529.459
• Hs Code.: 29339900
• Mol file: 1190307-88-0.mol

Synonyms:N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-methyl-P-phenyl-5'-uridylyl]-L-alanine 1-methylethyl ester;

Chemical Property of Sofosbuvir

Chemical Property:

• PKA: 9.39±0.10(Predicted)
• PSA: 167.99000
• Density: 1.4±0.1 g/cm³
• LogP: 2.04740
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)

Purity/Quality:

99%min ^*data from raw suppliers

Sofosbuvir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Sofosbuvir is a drug used for the treatment of hepatitis C. It is recommended to be used in combination with other drugs (such as velpatasvir) for the first-line treatment for HCV genotypes 1, 2, 3, 4, 5, and 6. It takes effect through acting as a nucleotide analog inhibitor, being capable of specially inhibiting the HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase.
• Uses: PSI-7977 is a phosphoramidate prodrug of PSI-7851, a nucleoside analog that, when phosphorylated, inhibits the RNA-dependent RNA polymerase of hepatitis C virus (EC50 = 92 nM). PSI-7977 is effective in vitro and in vivo.[Cayman Chemical] PSI-7977 is a prodrug that is metabolized to the active antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-monophosphate and is currently being investigated in phase 3 clinical trials for the t reatment of hepatitis C. Studies have profiled PSI-7977 as a nucleotide inhibitor of hepatitis C virus, exerting selective inhibitory effects towards HCV NS5B polymerase. PSI-7977 is a prodrug that is metabolized to the active antiviral agent 2''-deoxy-2''-α-fluoro-β-C-methyluridine-5''-monophosphate and is currently being investigated in phase 3 clinical trials for the treatment of hepatitis C. Studies have profiled PSI-7977 as a nucleotide inhibitor of hepatitis C virus, exerting selective inhibitory effects towards HCV NS5B polymerase.
• Clinical Use: In December 2013, sofosbuvir (also known as GS-7977 and PSI-7977) was approved in the United States for the treatment of hepatitis C virus (HCV) infection as a component of a combination antiviral treatment regimen. Sofosbuvir was discovered from an effort to enhance the activity of the parent nucleoside by bypassing rate-limiting monophosphorylation with a prodrug that would liberate the intactmonophosphate in the liver, where it would then be converted by cellular kinases to the active triphosphate species. In addition, the prodrug was designed to be amenable to oral delivery. In the initial synthesis of sofosbuvir, the iso-propyl ester of (L)-alanine was coupled with phenyl dichlorophosphate to provide a diastereomeric intermediate that was coupled with the uridine nucleoside. The diastereomeric mixture (GS-9851) was shown to produce high levels of triphosphate in vitro in primary hepatocytes and in the livers of rats, dogs, and monkeys after oral dosing. The individual diastereomers were obtained by chromatography or by crystallization. The diastereomer with the Sp configuration at the phosphorous center (sofosbuvir) was found to be >10-fold more potent in an HCV replicon assay than the corresponding Rp diastereomer (EC90s of 0.42 and 7.5 μM, respectively).
• Drug interactions: Potentially hazardous interactions with other drugs Anti-arrhythmics: possibly increased risk of bradycardia with amiodarone.

Technology Process of Sofosbuvir

There total 81 articles about Sofosbuvir which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

(S)-2-{[(1R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yI)-4-(R)-fluoro-3-(4-oxopentanoyl)-4-methyl-tetrahydrofuran-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid (S)-isopropyl ester → sofosbuvir (1190307-88-0,1496552-16-9)

Guidance literature:

With sodium sulfite; In tetrahydrofuran; water; at 20 ℃; for 4h;

Reference yield: 97.5%

2'-deoxy-2'-fluoro-2'-methyluridine (863329-66-2,2041584-99-8) + (S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester (1334513-02-8,1627824-09-2) → sofosbuvir (1190307-88-0,1496552-16-9)

Guidance literature:

With pyridine; aluminum (III) chloride; In dichloromethane; at 20 ℃; Reagent/catalyst; Temperature;

Reference yield: 93.0%

C18H26ClFNO7P + uracil (66-22-8,144104-68-7,18324-22-6,27072-01-1,2920-92-5,51953-19-6) → sofosbuvir (1190307-88-0,1496552-16-9)

Guidance literature:

uracil; With N,O-bis-(trimethylsilyl)-acetamide; In chlorobenzene; for 0.5h; Reflux;

C₁₈H₂₆ClFNO₇P; With tin(IV) chloride; In chlorobenzene; Reflux;

upstream raw materials:

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-[(R)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester

(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester

(S)-2-[(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester

Refernces

• 1、 -. "Preparation method of anti-HCV medicine". . . Retrieved 2021/06/13.
• 2、 -. "Method for carrying 3,3- diarylpropenal combined Grignard reagent to catalyze preparation of Soxavir (by machine translation)". Paragraph 0024-0032. . Retrieved 2020/05/30.