159326-68-8Relevant articles and documents
Cyanoamidine Cyclization Approach to Remdesivir's Nucleobase
Knapp, Rachel R.,Tona, Veronica,Okada, Taku,Sarpong, Richmond,Garg, Neil K.
, p. 8430 - 8435 (2020)
We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics.
Synthesis method of remdesivir intermediate triazinamine derivative
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Paragraph 0020; 0028; 0034; 0036; 0042, (2021/04/10)
The invention discloses a synthesis method of a remdesivir intermediate triazinamine derivative. The remdesivir intermediate triazinamine derivative is prepared by adopting a unique synthesis method. The invention solves the problems of expensive raw materials, large amount of wastewater in the production process and the like in existing reaction of a remdesivir intermediate triazinamine derivative, and provides the novel synthesis method of the remdesivir intermediate triazinamine derivative, wherein the synthesis method has the advantages of simple preparation method, cheap and easily available raw materials, greatly reduced production cost, less wastewater and the like; the synthesis method is never reported in the prior art, is a brand-new preparation method of the remdesivir intermediate triazinamine derivative, and provides a new synthesis idea for similar compounds of remdesivir.
Synthesis process of retegravir intermediate
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Paragraph 0005; 0024; 0025, (2021/03/11)
The invention relates to a synthesis process of a retegravir intermediate 7-iodine-4-amido pyrrolo [2,1-F] [1, 2, 4] triazine. The method comprises the following steps: by using pyrrole as an initialraw material, carrying out aldehyde groupintroduction through phosphorus oxychloride-DMF to obtain 2-aldehyde group pyrrole; preparing a 2-cyano key intermediate through ammonium sulfate, wherein thesteps is the key step of the process; cyclizing the cyano intermediate and formamidine acetate to prepare a 4-amino intermediate; reacting with NIS and adding iodine to prepare the target compound 7-iodine-4-amido pyrrolo [2,1-F] [1, 2, 4] triazine. The whole process has the advantages of simple and easily available raw materials, simple and easy operation, and very high economic value and socialbenefit.
Klein's Remdesivir-nucleobase synthesis revisited: Chemoselective cyanation of pyrrol-2-carboxaldehyde
Amarante, Giovanni W.,Pereira, Vinicius R. D.,da Silva, Adilson D.,dos Santos, Juliana A.
, p. 1391 - 1395 (2021/06/14)
4-Aminopyrrolo[2,1-f][1,2,4]triazine is a fundamental raw material in the synthesis of remdesivir, which demand has increased due to the tests and potential repositioning of this drug against Coronavirus disease 2019 (COVID-19). Here, three chemical steps route for the preparation of remdesivir's nucleobase is described. Particularly, a highly chemoselective cyanation of Klein's route and successful application of monochloramine prepared from commercial bleach as an N-amination reagent are presented.
Synthesis method of key intermediate 7-halogenated pyrrolo[1,2-F][1,2,4]triazin-4-amine of remdesivir
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Paragraph 0080-0082, (2021/08/14)
The invention discloses a synthesis method of a key intermediate 7-halogenated pyrrolo[1,2-F][1,2,4]triazin-4-amine of remdesivir as shown in a formula (h). Phthalimide is used as a raw material, and the key intermediate 7-halogenated pyrrolo[1,2-F][1,2,4]triazin-4-amine of remdesivir is synthesized through a series of reactions such as substitution, cyclization, bromination, cyano substitution, hydrazinolysis, heterocyclic ring synthesis and iodination . The post-treatment operation is optimized, and the method has the advantages of being short in reaction time, high in yield, suitable for industrial production and the like.
Preparation method of 4-aminopyrrolo[2,1-f][1,2,4]triazine
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Paragraph 0038-0044, (2021/10/11)
The invention discloses a preparation method of 4-aminopyrrolo[2,1-f][1,2,4]triazine, and belongs to the technical field of medicine synthesis. The method comprises the following steps: reacting 2,5-dimethoxytetrahydrofuran serving as a raw material with formylhydrazine to obtain formylamino pyrrole, then reacting formylamino pyrrole with cyanamide and a nucleophilic reagent in a polar solvent, and carrying out simple post-treatment and cyclization under the action of a catalyst to obtain 4-aminopyrrolo[2,1-f][1,2,4]triazine. The raw materials easy to obtain in the market are adopted, the whole process is easy and convenient to operate, the two-step yield is improved by improving an existing literature method, and development of a synthesis route conforming to industrialization is facilitated.
Process for synthesizing 7 -iodopyrrolo [2,F] [1,m-triazine -4 - amine
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Paragraph 0036-0039, (2021/11/21)
The invention belongs to the technical field of chemical synthesis of medicines, and relates to a synthesis process of 7-iodo pyrrolo [2, 1-F] [1, 2, 4] triazine-4-amine. According to the invention, 2, 5-dimethoxy tetrahydrofuran and acethydrazide are used as initial raw materials, and are subjected to substitution, cyanation, deacetylation, cyclization and iodination reactions to obtain 7-iodopyrrolo [2, 1-F] [1, 2, 4] triazine-4-amine. The preparation method is simple, the initial raw materials are 2, 5-dimethoxytetrahydrofuran and acethydrazide which are cheap and easy to obtain. Meanwhile,the yields of the first four steps all reach 85% or above, the productivity is also greatly improved, the total yield of the product is 50% or above, and the purity can reach 99% or above. And meanwhile, the intermediate product is good in quality, so that the dosage of formamidine acetate is reduced when the intermediate IV is prepared. Through experimental comparison, the route has obvious advantages compared with the traditional process route.
Novel synthesis method of compound 7-iodopyrrolo[2, 1-f][1, 2, 4]triazin-4-amine
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Paragraph 0049-0051, (2021/09/04)
The invention provides a method for preparing a triazine compound as shown in a formula (I). According to the invention, pyruvic acid and formamidine are taken as starting materials to synthesize an intermediate, and the intermediate is subjected to two-step reaction to obtain the compound shown in the formula (I). The method provided by the invention is mild in condition, simple and convenient to operate, capable of greatly reducing the cost and suitable for industrial mass production.
Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate
Xie, Yuanchao,Hu, Tianwen,Zhang, Yan,Wei, Daibao,Zheng, Wei,Zhu, Fuqiang,Tian, Guanghui,Aisa, Haji A.,Shen, Jingshan
, p. 5065 - 5072 (2021/04/12)
Currently, remdesivir is the first and only FDA-approved antiviral drug for COVID-19 treatment. Adequate supplies of remdesivir are highly warranted to cope with this global public health crisis. Herein, we report a Weinreb amide approach for preparing the key intermediate of remdesivir in the glycosylation step where overaddition side reactions are eliminated. Starting from 2,3,5-tri-O-benzyl-d-ribonolactone, the preferred route consisting of three sequential steps (Weinreb amidation, O-TMS protection, and Grignard addition) enables a high-yield (65%) synthesis of this intermediate at a kilogram scale. In particular, the undesirable PhMgCl used in previous methods was successfully replaced by MeMgBr. This approach proved to be suitable for the scalable production of the key remdesivir intermediate.
Preparation method of 4-aminopyrrolo [2, 1-f] [1, 2, 4] triazine
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Paragraph 0014-0018, (2021/04/03)
The invention relates to a preparation method of 4-amino pyrrolo [2, 1-f] [1, 2, 4] triazine, in particular to a method for efficiently synthesizing 4-amino pyrrolo [2, 1-f] [1, 2, 4] triazine by taking 1-amino-1H-pyrrole-2-carbonitrile hydrochloride and thiourea as raw materials through two steps of cyclization reaction and desulfurization reaction. The preparation method of the 4-aminopyrrolo [2, 1-f] [1, 2, 4] triazine is high in yield, low in cost, less in three wastes, good in product purity and suitable for industrialization.
