142217-69-4Relevant academic research and scientific papers
A novel and efficient synthesis of Entecavir
Liu, Xiaoyu,Jiao, Xiaozhen,Wu, Qian,Tian, Chengsen,Li, Renze,Xie, Ping
, p. 3805 - 3807 (2012)
A practical synthesis of Entecavir (1) has been accomplished in 10 steps with 21% overall yield. The key steps to construct the five-membered carbocyclic framework 2 are a ring-closing metathesis and a diethyl-aluminum 2,2,6,6-tetramethyl piperidide (DA-TMS) mediated epoxide isomerization. Furthermore, the guanine was introduced by modified Mitsunobu reaction.
Total Synthesis of Entecavir: A Robust Route for Pilot Production
Xu, Hua,Wang, Fang,Xue, Weicai,Zheng, Yunjie,Wang, Qi,Qiu, Fayang G.,Jin, Yehua
, p. 377 - 384 (2018)
A practical synthetic route for pilot production of entecavir is described. It is safe, robust, and scalable to kilogram scale. Starting from (S)-(+)-carvone, this synthetic route consists of a series of highly efficient reactions including a Favorskii rearrangement-elimination-epimerization sequence to establish the cyclopentene skeleton, the Baeyer-Villiger oxidation/rearrangement to afford the correct configuration of the secondary alcohol, and a directed homoallylic epoxidation followed by epoxide ring-opening to introduce the hydroxyl group suitable for the Mitsunobu reaction. In addition, the synthesis contains only four brief chromatographic purifications.
Novel preparation method and intermediates of entecavir
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, (2021/04/10)
The invention provides novel intermediates used for entecavir synthesis, compounds shown as a formula II and a formula III in the description, and a novel method for synthesizing entecavir by using the novel intermediates. When the novel intermediates are used for synthesizing entecavir, not only can the synthesis yield be remarkably improved, but also the production cost can be reduced.
Improved entecavir intermediate synthesis process and improved entecavir synthesis process
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, (2020/10/14)
The invention discloses an improved entecavir intermediate synthesis process and an improved entecavir synthesis process, and relates to the technical field of drug synthesis. The invention disclosesan improved entecavir intermediate synthesis process. In the synthesis process of an amino protection reaction product, amino protecting groups are added in batches; and the ratio of the reaction rawmaterials is optimized, so that the problems of long reaction time and relatively low amino protection reaction yield due to adoption of a one-time complete feeding mode in an existing synthesis modeare solved, the synthesis time of an amino protection reaction product is shortened to 50-70 minutes, and the obtained product is high in yield and purity. According to the improved entecavir synthesis process, in the amino protection reaction product synthesis process, reaction conditions are effectively optimized, and the purity of obtained entecavir reaches 99% or above.
Entecavir intermediate, synthetic method thereof and synthetic method of entecavir
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, (2020/07/29)
The invention belongs to the technical field of organic synthesis, and provides an entecavir intermediate, a synthesis method thereof and a method for synthesizing entecavir by using the entecavir intermediate. The intermediate and the methods have the advantages of easily available raw materials, low price, shortest synthesis steps, mild reaction conditions, easiness in control, simple equipmentrequirements, high total yield of products and easiness in industrial production.
Entecavir intermediate and synthesis method thereof as well as method for synthesis of entecavir
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Paragraph 0199; 0210-0211; 0216-0220, (2019/05/15)
The invention relates to an entecavir intermediate and a preparation method thereof and a method for synthesis of entecavir by using the intermediate. The methods for synthesis of the entecavir and the entecavir intermediate have the advantages of controllable chirality, high yield and high product purity, raw materials are wide in source, reagents are cheap and easily available, the reaction is simple, the operation is simple and convenient, green and environment-friendly effects are achieved, and the method is suitable for industrial large-scale production.
Method for synthesizing entecavir
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Paragraph 0040; 0060-0062; 0069, (2019/04/27)
The invention provides a method for synthesizing entecavir. The method comprises the steps of carrying out condensation ring-closure reaction, bromination addition reaction, reduction reaction, Witting reaction and the like. The method has the beneficial effects that the reaction raw material is easy to obtain, the reaction process is simple in operation, the requirement on reaction equipment is low, the reaction condition is relatively mild and the yield and the content are high.
A new scalable synthesis of entecavir
Gioti, Efthymia G.,Koftis, Theocharis V.,Neokosmidis, Efstratios,Vastardi, Elli,Kotoulas, Stefanos S.,Trakossas, Sakellarios,Tsatsas, Theodoros,Anagnostaki, Elizabeth E.,Panagiotidis, Theodoros D.,Zacharis, Constantinos,Tolika, Evanthia P.,Varvogli, Anastasia-Aikaterini,Andreou, Thanos,Gallos, John K.
, p. 519 - 527 (2017/12/29)
A new synthesis of entecavir from D-glucose in an average total yield of 3.5% was achieved via an intramolecular nitrile oxide cycloaddition (INOC) reaction and a Peterson olefination as key-steps. The present process was designed for industrial application, using widely available raw materials, simple and cheap reagents and avoiding low reaction temperatures, which are very common in the synthetic approaches towards similarly complex structures.
Entecavir industrial preparation method (by machine translation)
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, (2018/07/15)
The invention discloses entecavir industrial preparation method, which belongs to the technical field of organic synthesis. Including: Nysted reagent and intermediate VIII reaction, after the reaction is finished adding quenching fluid and holding the reaction system pH value of 7.0 - 8.5, obtained after the completion of reaction intermediates IX; intermediate IX react with hydrochloric acid, after the reaction is finished by adding the extractant and adjust pH value to 6.5 - 7.0, taking organic phase concentrated to 1/15 - 1/10 volume, crystallization, solid-liquid separation to obtain the intermediate X; intermediate with boron trichloride in dichloromethane in the X reaction, intermediate X with boron trichloride in a molar ratio of 1:5 - 10, the reaction temperature is - 30 — - 20 °C, after the reaction is finished cooling to - 30 °C following, dripping methanol, after the completion of the dropping the evaporation and once again by adding methanol, concentrated under reduced pressure, dryness and add into the water with the organic solvent of the extractant B, [...], adjust pH value to 6.5 - 7.0, concentrated, refine to get entecavir. (by machine translation)
SYNTHETIC METHOD OF ENTECAVIR AND INTERMEDIATE COMPOUNDS THEREOF
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Page/Page column 87, (2017/10/31)
The present invention relates to preparation method of drugs and intermediate compounds thereof, in particular, to preparation method of entecavir, intermediate compounds thereof and synthetic method of said intermediate compounds.
