- A Concise Route to MK-4482 (EIDD-2801) from Cytidine: Part 2
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A new route to MK-4482 was developed. The route replaces uridine with the more available and less expensive cytidine. Low-cost, simple reagents are used for the chemical transformations, and the yield is improved from 17% to 44%. A step is removed from the longest linear sequence, and these advancements are expected to expand access to MK-4482 should it become a viable drug substance.
- Gopalsamuthiram, Vijayagopal,Williams, Corshai,Noble, Jeffrey,Jamison, Timothy F.,Gupton, B. Frank,Snead, David R.
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- A High-Yielding Synthesis of EIDD-2801 from Uridine**
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A simple reordering of the reaction sequence allowed the improved synthesis of EIDD-2801, an antiviral drug with promising activity against the SARS-CoV-2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17 % to 61 %, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility.
- ?tv?s, Sándor B.,Dallinger, Doris,Kappe, C. Oliver,Snead, David R.,Steiner, Alexander,Znidar, Desiree
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- Preparation method of monabiravir
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The preparation method of monabiravir involves the field of medical technology. The method takes cytidine (1) as the starting material, after hydroxyl protection to obtain Compound 2; Compound 2 is obtained by isobutyryl chloride acylation to obtain a double-acylated intermediate 3, Compound 3 undergoes regional selective deacylation and hydroxylamineization tandem reaction to obtain Compound 4, and finally Compound 4 is deprotected, refined to obtain the finished monabiravir (5), the process route is as follows:
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- Conversion of: N- acyl amidines to amidoximes: A convenient synthetic approach to molnupiravir (EIDD-2801) from ribose
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An efficient method is described for the preparation of molnupiravir (EIDD-2801) an antiviral agent via regioselective conversion of an N-acyl-nucleoside intermediate, generated through stereo and regioselective glycosylation of protected ribose and N4-acetyl cytosine, to an amidoxime. This method avoids use of expensive starting materials, enzymes, complex reagents, and cumbersome purification procedures.
- Ahmed, Ajaz,Ahmed, Qazi Naveed,Mukherjee, Debaraj
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p. 36143 - 36147
(2021/12/04)
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- Preparation method of antiviral drug Molnupiravir
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The invention provides a preparation method of Molnupiravir, which comprises the steps of by using a compound 1 as an initial raw material, preparing a compound 4 by two methods, and finally carrying out acidolysis on the compound 4 by using a micro-channel reaction technique to obtain a Molnupiravir product 5. According to the method, esterification reaction and hydroxyamination reaction are optimized, conventional enzyme catalytic reaction is adopted in the esterification reaction, the yield is high, and three wastes are few; and in the hydroxyamination reaction, hydroxyamination is directly carried out by using a Bop reagent, so that the yield is improved, and the generation of three wastes is effectively reduced. The intermediate 4 is subjected to a micro-channel reaction technology, so that the acidolysis yield is increased, and the route efficiency is effectively improved. The reaction route is shown in the description.
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Paragraph 0058-0060
(2021/04/07)
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- Preparation method of 4-oximide-5'-(2-methylpropionyl) uridine
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The invention discloses a preparation method of 4-oximide-5'-(2-methylpropionyl) uridine, which comprises the following steps: S1, in the presence of acid, reacting a compound 1 with 2, 2-dimethoxypropane in an organic solvent to obtain a compound 2; S2, in the presence of an alkali, enabling the compound 2 to react in an organic solvent to obtain a compound 3; S3, reacting the compound 3 in an organic solvent in the presence of a hydroxylamine aqueous solution to obtain a compound 4; S4, reacting the compound 4 in an organic solvent in the presence of an acid to obtain a compound I; the solidwith good crystallization performance prepared by the method is simple in preparation condition and good in conversion rate and atom economy.
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Paragraph 0016
(2021/03/30)
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- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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- N4-HYDROXYCYTIDINE AND DERIVATIVES AND ANTI-VIRAL USES RELATED THERETO
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This disclosure relates to certain N4-hydroxycytidine derivatives, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of human coronavirus 2019-nCoV.
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- N4-HYDROXYCYTIDINE AND DERIVATIVES AND ANTI-VIRAL USES RELATED THERETO
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This disclosure relates to certain N4-hydroxycytidine derivatives, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections, such as Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infection with the disclosed compounds.
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- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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