879551-04-9Relevant articles and documents
BI- AND MONOCYCLIC NUCLEOSIDE ANALOGS FOR TREATMENT OF HEPATITIS E
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, (2021/10/22)
The present disclosure is directed toward bi- and monocyclic nucleoside analogs, and compositions comprising these compounds for use in the treatment of hepatitis E infections.
Method for preparing 3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-one
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Paragraph 0020-0044, (2020/11/05)
The invention discloses a method for preparing 3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-one, comprising the following steps that: ((2R, 3R, 4R)-3-(benzyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl) methyl benzoate is dispersed in an organic solvent, excessive strong acid is added for heating reflux, the organic solvent is removed, and pulping, filtering and drying are performed, wherein the strong acid is methanesulfonic acid, sulfuric acid, trifluoromethanesulfonic acid or concentrated hydrochloric acid. ((2R, 3R, 4R)-3-(benzyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl) methyl benzoate is adopted as a raw material to be subjected to a reflux reaction with excessive specific strong acid, a high-purity and high-yield product can be obtained only through a one-step reaction, the process steps are simple, and mass production of the product is facilitated.
PROCESS FOR PREPARATION OF LACTONE DERIVATIVES AND INTERMEDIATES THEREOF
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Page/Page column 36; 37, (2018/03/09)
A novel process for the preparation of lactone derivatives, and intermediates thereof is described. The lactone derivatives are important precursors for the synthesis of anti-hepatitis C virus agents, including sofosbuvir.
Preparation method of sofosbuvir intermediate
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Paragraph 0108; 0109; 0112; 0113; 0116; 0117, (2018/03/01)
The invention discloses a preparation method of a sofosbuvir intermediate of (2R)-2-deoxy-2-fluoro-2-methyl-D-erythro-pentonic acid-g-lactone 3,5-dibenzoate. The intermediate structure corresponds toa formula I shown as the description. The method comprises the step that the sofosbuvir intermediate shown as the formula I is finally obtained by using (D2) (S)-(+)-4-phenyl-2-oxazolidinone of a compound shown as a formula II as a raw material through six-step reaction of condensation, fluorination, Adol addition, oxidation cyclization, isomerization and benzoylation. The preparation method hasthe advantages that the raw materials are cheap and can be easily obtained; the reaction conditions are mild; the route is short; the yield is high; three wastes are few; the pollution is little; thepreparation method is suitable for industrial production.
Synthesizing method for drug intermediate
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Paragraph 0103-0106; 0111-0113; 0117-0119, (2017/06/02)
The invention discloses a synthesizing method for a drug intermediate, and relates to the field of drug synthesis, in particular to the field of organic synthesis. In the synthesizing method, compound V(4S,5R)-ethyl-5-((R)-2,2-dimethyl-1,3-dioxolame-4-base)-4-methyl-1,3,2-dioxathiolane-4- carboxylic acid-2,2'dioxide serves as a raw material, a compound II is prepared through three synthesizing methods, and an intermediate compound I is prepared through the compound II. The provided synthesizing technology has the beneficial effects that cost is low, few byproducts are generated, the yield is high, and pollution to the environment is weak.
Preparation for sofosbuvir key intermediate
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Paragraph 0017; 0018, (2016/10/20)
The invention relates to preparation for a sofosbuvir key intermediate. With (E)-(S)-3-(2,2-dimethyl-1,3-dioxolane-4-base)-2-ethyl methacrylate being an initial raw material, preparation of 3,5-bis-O-benzoyl-2-deoxidation-2-fluorine-2-C-methyl-D-riboic acid-gamma-lactone is achieved through an epoxidation reaction, fluoridation, a de-acetonylidene cyclization reaction and a benzoyl reaction. According to the method, a synthesis route is short, and in the reaction process, a reagent that oxidability is high, and in the aftertreatment process, potassium permanganate or sodium permanganate and high-corrosivity SOCl2 deep in waste water color will generate a lot of waste water will not be involved.
Preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone
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Paragraph 0030; 0054, (2017/06/02)
The invention discloses a preparation method for 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method comprises the following steps: subjecting a starting raw material D-mannitol to acetone protection and sodium periodate oxidation; then subjecting the treated D-mannitol and a self-made ylide reagent to the Witting reaction; then carrying out selective oxidation by using an aqueous sodium permanganate solution; then successively carrying out sulfonylation, fluorination with potassium fluoride, and ring closing with a concentrated protective group protective group; protecting the hydroxyl group by using benzoyl chloride; and then carrying out purification so as to obtain the final product 3,5-dibenzoyl-2-deoxy-2-fluoro-2-methyl-D-ribono-gamma-lactone. The preparation method provided by the invention uses easily available and cheap raw materials, so production cost is greatly reduced; and the operation of the preparation method is coherent and simple, and the quantity of waste gas, waste water and industrial residues is lower than the quantity of waste gas, waste water and industrial residues reported in the prior art.
Method for preparing intermediate of Sofosbuvir
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, (2016/12/26)
The invention provides a method for preparing 3,5-bis-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-D-ribose-gamma-lactone of D-ribofuranose lactone (structural formula 1). The compound is an important intermediate of a hepatitis C virus (HCV) NS5B polymerase inhibitor Sofosbuvir. The formula 1 is shown in the specification.
PRODUCTION METHOD OF (2R)-2-FLUORO-2-C-METHYL-D-RIBONO-γ-LACTONE
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Paragraph 0116; 0117; 0118, (2016/11/07)
PROBLEM TO BE SOLVED: To provide a production method of (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone. SOLUTION: A (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone precursor containing various diastereomers can be produced by performing Reformatsky reaction using activated metal to a 2-fluoro-2-halopropionate derivative and a D-glyceraldehyde derivative. The obtained mixture containing the (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone precursor is subjected to deprotection and lactonizing under an acidic condition, is converted to a diastereomer mixture containing 2-fluoro-2-C-methyl-D-ribono-γ-lactone and is recrystallized, thereby inducing the mixture to (2R)-2-fluoro-2-C-methyl-D-ribono-γ-lactone. COPYRIGHT: (C)2015,JPOandINPIT
(2R)-2-DEOXY-2,2-DISUBSTITUTED-RIBONO-1,4-LACTONE AND PREPARATION METHOD AND USE THEREOF
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Paragraph 0064; 0065; 0066, (2015/11/02)
This invention disclose (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone in a single configuration and preparation method and use thereof. The (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone, or a pharmaceutically acceptable salt, an ester, a prodrug or a solvate thereof according to the invention are important intermediates of a variety of anti-viral and anti-tumor active ingredients. A compound obtained from (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone via an acylation reaction can be directly used for preparing various anti-viral and anti-tumor drugs. The Chiral synthesis method and the spontaneous resolution method of the compound of (2R)-2-deoxy-2,2-disubstituted-ribono-1,4-lactone according to the invention have the following advantages: the reaction routes are short and simple with high yield and low cost, which are suitable for industrial application.