1496552-16-9

Usage

Uses

Used in Pharmaceutical Industry:
D-Alanine, N-[[P(R),2'R]-2'-deoxy-2'-fluoro-2'-Methyl-P-phenyl-5'-uridylyl]-, 1-Methylethyl ester is used as a synthetic intermediate for the production of specific pharmaceuticals, given its complex structure and the presence of a D-Alanine residue, which is an essential component in many biologically active molecules.
Used in Biochemical Research:
In the field of biochemical research, D-Alanine, N-[[P(R),2'R]-2'-deoxy-2'-fluoro-2'-Methyl-P-phenyl-5'-uridylyl]-, 1-Methylethyl ester may be employed as a research tool to study the interactions and effects of modified nucleotides and their derivatives on biological systems, potentially leading to new insights in molecular biology and drug development.

Upstream product

• 863329-66-2 2'-deoxy-2'-fluoro-2'-methyluridine 
• 770-12-7 O-phenyl phosphorodichloridate 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 863329-65-1 (2‘R)-2‘-deoxy-2’-fluoro-2-methyluridine-3’,5’-dibenzoate 
• 817204-32-3 (2R,3R,4R,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-((benzoyloxy)methyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate 
• 261909-49-3 phenyl(isopropoxy-L-alaninyl) phosphorochloridate 
• 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 
• 1064684-44-1 sofosbuvir 
• 39825-33-7 isopropyl L-alanine 
• 1334513-02-8 (S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester 

Relevant academic research and scientific papers

Preparation method of anti-HCV medicine

The invention relates to the technical field of medical intermediates, in particular to a preparation method of an anti-HCV drug, which comprises the following steps: 1) reacting a compound I with a compound II in the presence of Lewis acid and alkali to obtain a compound III; and 2) reacting the compound III with a compound IV to obtain a compound V. The method effectively solves the problems of tedious steps, difficulty in purification, high cost and the like in the prior art. Meanwhile, the whole route is mild in reaction condition, convenient to operate, high in yield and purity and suitable for industrial large-scale production.

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.

Method for synthesizing Sofosbuvir

The invention discloses a method for synthesizing Sofosbuvir. The method comprises the steps of adding a compound 1, a compound 2 and dichloromethane into a reaction bulb, cooling the temperature to 0DEG C, then, adding aluminum chloride, adding a proper amount of pyridine, and carrying out a reaction at a reaction temperature of 15 DEG C to 20 DEG C, thereby producing the Sofosbuvir. According to the method, the reaction is high in conversion ratio and good in regioselectivity and stereoselectivity, so that the synthesis cost of the Sofosbuvir is reduced, and the method has remarkable socialand economic benefits.

Method for carrying 3,3- diarylpropenal combined Grignard reagent to catalyze preparation of Soxavir (by machine translation)

To the method, 3,3 - compound, is subjected to catalytic activation: and compound 2 to be subjected to catalytic activation, and the method, is used for catalyzing and activating compound 3 with 1 diarylpropenal and Grignard reagent; so that product yield and purity: can be reduced 3,3 - by two-substitution by-product generation process. 2. (by machine translation)

Synthesis and evaluation of 2′-dihalo ribonucleotide prodrugs with activity against hepatitis C virus

[Figure presented] Hepatitis C virus (HCV) nucleoside inhibitors have been a key focus of nearly 2 decades of HCV drug research due to a high barrier to drug resistance and pan-genotypic activity profile provided by molecules in this drug class. Our investigations focused on several potent 2′-halogenated uridine-based HCV polymerase inhibitors, resulting in the discovery of novel 2′-deoxy-2′-dihalo-uridine analogs that are potent inhibitors in replicon assays for all genotypes. Further studies to improve in vivo performance of these nucleoside inhibitors identified aminoisobutyric acid ethyl ester (AIBEE) phosphoramidate prodrugs 18a and 18c, which provide high levels of the active triphosphate in dog liver. AIBEE prodrug 18c was compared with sofosbuvir (1) by co-dosing both compounds by oral administration in dog (5 mg/kg each) and measuring liver concentrations of the active triphosphate metabolite at both 4 and 24 h post dosing. In this study, 18c provided liver triphosphate concentrations that were 6-fold higher than sofosbuvir (1) at both biopsy time points, suggesting that 18c could be a highly effective agent for treating HCV infected patients in the clinic.

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.

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.

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%.

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.

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