- REMDESIVIR INTERMEDIATES
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The present invention relates to a process for the preparation of a compound of formula (I) and to novel intermediates of the synthesis, wherein X is hydrogen, bromine or iodine; R1 is a protecting group, R2 is hydrogen or a protecting group, and PG is a protecting group.
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- METHODS OF PREPARING 1'-CYANO NUCLEOSIDES
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The present disclosure generally describes methods of preparing l'-cyano nucleosides, such as a compound of Formula (I). For example, the compound of Formula (I) can be prepared from a compound of Formula (Il-a) in a flow reactor.
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- N-protected heterocyclic compound, preparation method thereof and method for preparing C-nucleoside derivative by using N-protected heterocyclic compound
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The invention provides an N-protected heterocyclic compound, a preparation method thereof and a method for preparing a C-nucleoside derivative by using the N-protected heterocyclic compound. Specifically, the invention provides a method for preparing the C-nucleoside derivative by using a heterocyclic compound protected by N-carbobenzoxy or N-tert-butyloxycarboryl. According to the method, halogenation is not needed, temporary amino protection is not needed, protons of the heterocyclic compound are removed by directly using an organic lithium or organic magnesium compound, and addition with ribose lactone is carried out. According to the method, the synthesis route of the C-nucleoside derivative is shortened, and the yield of the reaction of the heterocyclic compound and the ribose lactone is remarkably improved under the condition that no halogen atom is used as a substituent group.
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Paragraph 0430; 0431; 04329
(2021/08/14)
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- Synthesis method of key intermediate of ridecevir
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The invention provides a novel method for preparing a key intermediate of ridecevir as shown in a formula (VII). Benzyl fully-protected lactone as shown in a formula (I) is used as a starting material and is subjected to ring opening to obtain a compound as shown in a formula (II). The hydroxyl of the compound (II) is protected by a proper protecting group to obtain the compound shown in the formula (III). The compound (III) and the compound (IV) are subjected to coupling, protecting group removal and cyclization to obtain an intermediate shown as a formula (V) by a one-pot method. The intermediate (V) is subjected to two-step conversion to obtain the key intermediate (VII) of the ridecevir. According to the method provided by the invention, the compound (I) which can be bought in the market is used as the starting material, and the key intermediate compound (VII) for preparing the ridecevir is obtained at high yield through five-step reaction, so that the cost is greatly reduced, and the method is suitable for industrial mass production.
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- Novel compound and application thereof
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The invention relates to a novel compound and application thereof, and also relates to an application of the compound in preparation of antiviral drugs and the like. In particular, AIDS virus is present. Application of hepatitis B virus, paramyxovirus and
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Paragraph 0089-0091
(2021/09/08)
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- Method for preparing retegravir by using micro-channel reactor
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The invention discloses a method for synthesizing retegravir by using a micro-channel reactor, which realizes continuous flow synthesis of retegravir by using a scale effect of a micro-flow field technology and using a novel micro-channel reactor to repla
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Paragraph 0087-0095; 0115
(2021/04/21)
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- Synthesis method of antiviral drug ridexivir and intermediate thereof
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The invention discloses a synthesis method of an antiviral drug retegravir, which comprises the following steps: carrying out addition reaction on a compound 1 and a compound 2 to obtain a compound 3,carrying out cyanation reaction under the action of Lewis acid to obtain a compound 4, carrying out copper-catalyzed ammonolysis reaction to obtain a compound 5, carrying out palladium-catalyzed hydrogenation debenzylation to obtain a compound 6, and finally, reacting with a compound 7 to obtain a retegravir product. According to the method, the compound 1 is directly used as a raw material, no extra active hydrogen exists, and the reaction yield is high,the method has the advantages of simple operation, no amino interference, high cyanation reaction yield, clean and efficient palladium-carbon alkylation debenzylation reaction, convenient palladium-carbon recovery, and less three wastes. In addition, the leaving group of the compound 7 is improved to improve the activity of the compound 7, and the unprotected docking reaction of 6 and 7 is optimized by adding a proper auxiliary agent, so that the selectivity and the reaction yield can be greatly improved. The route is simple to operate, high in total yield, high in product purity and suitable for large-scale production.
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- Method for continuously preparing retegravir intermediate by using micro-channel reactor
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The invention discloses a method for continuously preparing a retegravir intermediate (2R, 3R, 4R, 5R)-2- (4-aminopyrrolo [2, 1-f] [1, 2, 4] triazine- 7-yl)-3, 4-bis (benzyloxy)-5 -((benzyloxy)methyl)tetrahydrofuran- 2-nitrile by using a micro-channel rea
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Paragraph 0031; 0040; 0042-0090
(2021/01/30)
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- Preparation method of retegravir intermediate
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The invention relates to the technical field of medical intermediates, in particular to a preparation method of a retegravir intermediate. The chemical name of the compound is (2R, 3R, 4R, 5R)-2-(4-aminopyrrole [2, 1-f] [1, 2, 4] triazine-7-yl)-3, 4, 5, 6
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Paragraph 0030; 0034-0036; 0040-0041
(2020/06/16)
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- Novel compound for preparing key intermediate of remdesivir and preparation method thereof
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The invention relates to a novel compound II used for synthesizing a key intermediate of remdesivir and a preparation method thereof. The preparation method of the compound II comprises the followingsteps: (a) halogenating 4-X-pyrrole[2,1-f][1,2,4]triazine as shown in a formula (V) to obtain 4-X-7-halogenated-pyrrole[2,1-f][1,2,4]triazine as shown in a formula (IV); (b) adding magnesium or alkylmagnesium halide to react with a ribose lactone derivative shown in the formula (VI) to generate glycosylate shown in the formula (III); and (c) converting hydroxyl into cyano in a proper solvent by the glycosylate (III) under the action of a cyaniding agent, a Lewis acid and a Bronsted acid to obtain the compound II. The prepared compound can be used for generating a key intermediate I required in synthesis of remdesivir through an ammoniation reaction. The invention provides a new compound II and a process route which is different from the prior art, is high in reaction selectivity and can be used for preparing the remdesivir key intermediate in batches.
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- Development of a Large-Scale Cyanation Process Using Continuous Flow Chemistry en Route to the Synthesis of Remdesivir
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The implementation of cyanation chemistry at manufacturing scales using batch equipment can be challenging because of the hazardous nature of the reagents employed and the tight control of reaction parameters, including cryogenic temperatures, that help t
- Badalov, Pavel,Chtchemelinine, Andrei,Gao, Detian,Heumann, Lars,Stevens, Andrew C.,Vieira, Tiago
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p. 2113 - 2121
(2020/11/23)
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- Preparation method of nucleoside analogue
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The invention belongs to the technical field of chemical synthesis, and specifically relates to a new preparation method of (2R,3R,4S,5R)-2-(4-aminopyrrolo[1,2-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-carbonitrile. The metho
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Paragraph 0030-0038
(2020/02/29)
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- METHODS FOR TREATING FILOVIRIDAE VIRUS INFECTIONS
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Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae vims infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula (IV): The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.
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- Practical synthesis of 1′-substituted Tubercidin C-nucleoside analogs
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Several 1′-substituted analogs of Tubercidin C-nucleosides were prepared using a highly convergent synthesis. Good to high diastereoselectivity was achieved using a variety of nucleophiles targeting the 1′-position. The source for this stereoselectivity i
- Metobo, Sammy E.,Xu, Jie,Saunders, Oliver L.,Butler, Thomas,Aktoudianakis, Evangelos,Cho, Aesop,Kim, Choung U.
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p. 484 - 486
(2012/02/02)
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- Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides
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A series of 1′-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R = CN was attributed to inhibition of HCV NS5B polymerase and intracellular concentration of the corresponding nucleoside triphosphate.
- Cho, Aesop,Saunders, Oliver L.,Butler, Thomas,Zhang, Lijun,Xu, Jie,Vela, Jennifer E.,Feng, Joy Y.,Ray, Adrian S.,Kim, Choung U.
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p. 2705 - 2707
(2012/05/20)
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