198904-85-7Relevant articles and documents
A scalable synthesis of biaryl unit of the HIV protease inhibitor atazanavir
Katari, Naresh K.,Prasad, Malavattu G.,Reddy, Pedavenkatagari N.,Vijayalakshmi, Chapala
, p. 68 - 72 (2020/01/23)
Atazanavir is one of the most prescribed HIV-1 protease inhibitors approved by the FDA. It was the first protease inhibitor approved for once-a-day dosing to treat AIDS due to good oral bioa-vailability and favorable pharmacokinetic profile. This research aims to develop a new synthetic cost effective process for biaryl-hydrazine unit {tert-butyl 2-[4-(2-pyridinyl)benzyl]hydrazinecarboxylate} of atazanavir on a large scale. The synthesis involved palladium catalyzed Suzuki-Miyaura coupling of 2-chloropyridine and (4-cyanophenyl)boronic acid followed by DIBAL-H reduction of cyano group to aldehyde which is then treated with tert-butyl carbazate to furnish hydrazone subsequently in situ reduction with NaBH4. A large scale synthesis of biaryl-hydrazine unit of atazanavir was accomplished in three steps with 71% overall yield. We have developed a short and efficient synthesis of atazanavir key intermediate biaryl-hydrazine unit. The process does not require the usage of Grignard reagent, expensive catalyst, protection/deprotection of aldehyde moiety and catalytic hydrogenation.
Industrial production method of atazanavir intermediate tert-butyl 2-[4-(2-pyridyl)benzyl]-carbazate
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Paragraph 0035; 0045-0047; 0048; 0058-0060, (2019/04/17)
The invention relates to the technical field of biological industry, in particular to an industrial production method of atazanavir intermediate tert-butyl 2-[4-(2-pyridyl)benzyl]-carbazate. The industrial production method includes: subjecting p-chlorobenzaldehyde as a raw material to aldolization, carrying out Grignard coupling reaction, carrying out reductive amination to generate phenylhydrazone, and carrying out hydrogenation to obtain the target product tert-butyl 2-[4-(2-pyridyl)benzyl]-carbazate. Compared with the prior art, the industrial production method has the advantages of high efficiency, good stability, low cost, good operational convenience and the like, and is suitable for continuous production of high-quality products, with product purity reaching 99% and above and unknow impurity content less than 0.3%.
Preparation method of tert-butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate
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Paragraph 0042; 0043, (2017/05/23)
The invention discloses a preparation method of tert-butyl 2-(4-(pyridin-2-yl)benzyl)hydrazinecarboxylate. The preparation method comprises the steps that 1, 4-(2-pyridyl)benzaldehyde, ethyl alcohol and tert-butyl carbazate are put into a reaction kettle, and stirring is started; 2, tert-butyl 2-2-[4-(2-pyridyl)benzal]hydrazinecarboxylate is obtained; 3, tert-butyl 2-2-[4-(2-pyridyl)benzal]hydrazinecarboxylate, ethyl alcohol and palladium carbon are put into the reaction kettle, and stirring is started; 4, a sodium formate solution is dropwise added into a solution obtained in the step 3; 5, after a reaction is completed, a finished product is obtained. The preparation method has the following advantages that the production steps are greatly reduced compared with the prior art, and meanwhile a produced by-product is single and easy to separate; absolute ethyl alcohol serving as a solvent can be recycled repeatedly, palladium carbon serving as a catalyst can be used multiple times through recycling and draining, the production cost is lowered, and the production benefit of an enterprise is improved.
Synthesis and biological evaluation of Hydrazone derivatives as antifungal agents
Casanova, Bruna B.,Muniz, Mauro N.,De Oliveira, Thayse,De Oliveira, Luís Flavio,Machado, Michel M.,Fuentefria, Alexandre M.,Gosmann, Grace,Gnoatto, Simone C. B.
, p. 9229 - 9241 (2016/08/31)
Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-Toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C.Tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-Trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 μg/mL and 8-16 μg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.
Reductive alkylation of hydrazine derivatives with α-picoline-borane and its applications to the syntheses of useful compounds related to active pharmaceutical ingredients
Kawase, Yasushi,Yamagishi, Takehiro,Kato, Jun-Ya,Kutsuma, Teruo,Kataoka, Tadashi,Iwakuma, Takeo,Yokomatsu, Tsutomu
, p. 455 - 464 (2014/03/21)
An efficient method for the direct reductive alkylation of hydrazine derivatives with α-picoline-borane has been developed to synthesize a variety of N-alkylhydrazine derivatives. This method provided N,N-dialkylhydrazine derivatives and N-monoalkylhydrazine derivatives upon fine-tuning of the substrates and the reagent equivalency in a one-pot manner. The method was applied to the synthesis of active pharmaceutical ingredients of therapeutic drugs such as isocarboxazid.
A three step continuous flow synthesis of the biaryl unit of the HIV protease inhibitor Atazanavir
Dalla-Vechia, Luciana,Reichart, Benedikt,Glasnov, Toma,Miranda, Leandro S. M.,Kappe, C. Oliver,De Souza, Rodrigo O. M. A.
, p. 6806 - 6813 (2013/10/01)
The development of multistep continuous flow reactions for the synthesis of important intermediates for the pharmaceutical industry is still a significant challenge. In the present contribution the biaryl-hydrazine unit of Atazanavir, an important HIV protease inhibitor, was prepared in a three-step continuous flow sequence in 74% overall yield. The synthesis involved Pd-catalyzed Suzuki-Miyaura cross-coupling, followed by hydrazone formation and a subsequent hydrogenation step, and additionally incorporates a liquid-liquid extraction step.
PROCESS FOR THE PREPARATION OF ARYLPYRIDINYL COMPOUNDS
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Page/Page column 15, (2011/01/12)
A process is described for the preparation of arylpyridine compounds by aryl-aryl cross-coupling reactions between a halopyridine and an arylmagnesium halide carried out in the presence of a catalytic amount of a zinc salt and a catalytic amount of palladium complex with a bidentate phosphine. The zinc salt is preferably selected from ZnCl2, ZnBr2 and/or Zn(OAc)2, while the palladium complex with a bidentate phosphine is preferably selected from the group of (1,2-Bis(diphenylphosphino)ethane)palladium(II) chloride, (1,3-Bis(diphenylphosphino)propane) palladium(II) chloride and (1,4-Bis(diphenylphosphino)butane)palladium(II) chloride. Most preferred is (1,2-Bis(diphenylphosphino)ethane)palladium(II) chloride. It is thus possible to obtain molar yields higher than 95% calculated on the arylmagnesium halide and a catalyticity less than 1 : 1500. The process is particularly suitable for the preparation of 4-(2'-pyridyl)benzaldehyde which can then effectively been converted to N1-(t-butoxycarbonyl)-N2-(4-(2'pyridyl)benzyl)hydrazine.
Azapeptide derivatives as HIV protease inhibitors
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Page/Page column 33, (2009/01/24)
This invention relates to novel compounds of the Formula Ib: that are azapeptides, and pharmaceutically acceptable salts thereof. More specifically, the invention relates to novel azapeptide compounds that are derivatives of the HIV protease inhibitor atazanavir sulfate. This invention also provides pyrogen-free compositions comprising one or more compounds of the invention and a carrier, and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are treated by administering HIV protease inhibitors. The invention also relates to the use of one or more of the disclosed compounds as reagents in analytical studies involving atazanavir.
HIV PROTEASE INHIBITING COMPOUNDS
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Page/Page column 113, (2010/02/12)
A compound of the formula (I) is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
HIV PROTEASE INHIBITING COMPOUNDS
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Page/Page column 58, (2010/02/12)
A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
