- Enantioselective epoxidation by the chiral auxiliary approach: Asymmetric total synthesis of (+)-Ambrisentan
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Enantioselective and a highly concise total synthesis of Ambrisentan are described. The chiral auxiliary controlled enantioselective epoxidation (Azerad protocol), photochemical regioselective epoxide opening, and base mediated ester hydrolysis reactions
- Madhu, Madasu,Doda, Sai Reddy,Begari, Prem Kumar,Dasari, Krishna Rao,Thalari, Gangadhar,Kadari, Sudhakar,Yadav, Jhillu Singh
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p. 942 - 946
(2021/02/26)
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- An improved method of preparing Anritsu tezosentan
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The invention belongs to the field of chemical synthesis, and discloses an improved method used for preparing ambrisentan. According to the improved method, 2-hydroxy-3-methoxy-3,3-diphenylpropionic ester and 4,6-dimethyl-2-methylsulfonylpyrimidine are su
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- Preparation method of ambrisentan
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The invention belongs to the field of medicine synthesis and particularly relates to a preparation method of ambrisentan, wherein the ambrisentan is prepared through a benzyl protection reaction, a condensation reaction, and a benzyl protection group removal reaction in the method. A benzyl-protected intermediate is delivered to the next step of the condensation reaction without post-treatment. The debenzylation reaction is carried out through catalytic hydrogenation, which is green and environment-friendly and is simple in reaction operations and post-treatment. A reaction liquid is treated and pulped in an ether solvent, so that residual raw materials and intermediate in the solid are removed effectively. When an ambrisentan crude product is prepared, a recrystallization step with a methanol/water mixed solvent is carried out to obtain high-purity ambrisentan. The method is fewer in steps and high in yield, has short production cycle, simple operation, good reproducibility and mild conditions, and is suitable for industrial production.
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Paragraph 0056-0064
(2019/05/15)
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- Process Research for (+)-Ambrisentan, an Endothelin-A Receptor Antagonist
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An efficient and robust synthetic route to (+)-ambrisentan ((+)-AMB) was designed by recycling the unwanted isomer from the resolution mother liquors. The racemization of AMB in the absence of either acid or base in the given solvents was reported. The recovery process was developed to produce racemates with purities over 99.5%. The mechanism of the formation of the process-related impurities of (+)-AMB is also discussed in detail. (+)-AMB was obtained in 47% overall yield with >99.5% purity and 99.8% e.e. by chiral resolution with only one recycling of the mother liquors on a 100-g scale without column purification.
- Feng, Wei-Dong,Zhuo, Song-Ming,Yu, Jun,Zhao, Chuan-Meng,Zhang, Fu-Li
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p. 1200 - 1207
(2018/09/06)
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- METHOD FOR PRODUCING (S)-2-HYDROXYPROPANOIC ACID DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a method for producing an (S)-2-hydroxypropanoic acid derivative and ambrisentan having high optical purity in an industrially advantageous manner. SOLUTION: There is provided a method for producing an (S)-2-hydroxypropanoic acid derivative represented by the formula (1a) by reacting an (RS)-2-hydroxypropanoic acid derivative represented by the formula (1) with (S)-(+)-1,2,3,4-tetrahydro-1-naphthylamine to form a diastereomer salt, followed by desalting. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0005; 0047
(2017/12/15)
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- Process for Preparing Ambrisentan
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The present invention relates to a method of preparing high purity ambrisentan in a cost-effective and efficient way, and a novel intermediate product used for the method. According to the present invention, optical resolution of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid can be cost-effectively and efficiently performed using L-prolinamide, and thus crystalline ambrisentan having 99.9% or more of purity and optical purity can be prepared on an industrial scale using the same.COPYRIGHT KIPO 2016
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- Process for the Preparation of an Endothelin Receptor Antagonist
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The present invention relates to a novel process for the preparation of a compound of formula (I) wherein R is a methyl or methoxy group; to certain novel intermediates prepared in such a process and their use.
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Page/Page column
(2014/09/29)
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- Method for Preparing Optically Pure (+)-Ambrisentan and (+)-Darusentan
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Disclosed is a method for preparing optically pure (+)-ambrisentan and (+)-darusentan, comprising: firstly catalyzing the asymmetric epoxidation of a β-unsaturated alkene using a chiral ketone derived from fructose or a hydrate thereof as a catalyst, and then subjecting the product to an epoxy compound ring-opening reaction and substitution reaction successively to obtain optically pure (+)-ambrisentan and (+)-darusentan.
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- PROCESS FOR THE PREPARATION OF AN ENDOTHELIN RECEPTOR ANTAGONIST
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The present invention relates to a novel process for the preparation of a compound of formula (I) wherein R is a methyl or methoxy group; to certain novel intermediates prepared in such a process and their use.
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- PROCESS FOR THE PREPARATION OF HIGHLY PURE AMBRISENTAN
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The present invention relates to an improved and novel process for the preparation of highly pure (>99.8%) (+)-2(S)-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropionic acid (Ambrisentan) of formula (I).
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Paragraph 0057; 0058; 0059
(2013/03/26)
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- PROCESS FOR THE PREPARATION OF AMBRISENTAN AND NOVEL INTERMEDIATES THEREOF
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The invention relates to improved processes for the preparation of ambrisentan. The invention also relates to a novel intermediate useful in the preparation of ambrisentan and a process for the preparation of the intermediate. The invention also relates to new polymorphic form of ambrisentan. In particular, it relates to a polymorphic form, designated as Form I of ambrisentan and a process for the preparation of the Form I.
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Page/Page column 7
(2012/07/28)
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- Stable solid salts of ambrisentan
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New solid salts of ambrisentan, including the phosphate salt, ambrisentan sodium salt and ambrisentan tert-butylammonium salt, in crystalline, amorphous, anhydrous or hydrated form.
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Page/Page column 4
(2012/07/28)
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- Synthesis of (+)-ambrisentan via chiral ketone-catalyzed asymmetric epoxidation
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The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3-diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxi
- Peng, Xianyou,Li, Peijun,Shi, Yian
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p. 701 - 703
(2012/03/26)
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- IMPROVED PROCESS FOR THE PREPARATION OF AMBRISENTAN AND NOVEL INTERMEDIATES THEREOF
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The invention relates to improved processes for the preparation of ambrisentan. The invention also relates to a novel intermediate useful in the preparation of ambrisentan and a process for the preparation of the intermediate. The invention also relates to new polymorphic form of ambrisentan. In particular, it relates to a polymorphic form, designated as Form I of ambrisentan and a process for the preparation of the Form I.
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Page/Page column 23
(2011/02/24)
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- Improved Process For The Preparation Of Endothelin Receptor Antagonists
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The present invention relates to improved processes for the preparation of Endothelin receptor antagonists, their salts and intermediates.
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- A PROCESS FOR THE PREPARATION OF HIGHLY PURE AMBRISENTAN
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The present invention relates to an improved and novel process for the preparation of highly pure (>99.8 %) (+)-2(S)-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropionic acid (Ambrisentan) of formula (I).
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Page/Page column 8-9
(2011/10/10)
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- IMPROVED PROCESS FOR THE PREPARATION OF ENDOTHELIN RECEPTOR ANTAGONISTS
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The present invention relates to improved processes for the preparation of Endothelin receptor antagonists, their salts and intermediates.
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Page/Page column 27
(2010/08/05)
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- Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists
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A novel class of endothelin-A receptor ligands was discovered by high-throughput screening. Lead structure optimization led to highly potent antagonists which can be synthesized in a short sequence. The compounds are endothelin-A-selective, are orally available, and show a long duration of action.
- Riechers, Hartmut,Albrecht, Hans-Peter,Amberg, Willi,Baumann, Ernst,Bernard, Harald,B?hm, Hans-Joachim,Klinge, Dagmar,Kling, Andreas,Müller, Stefan,Raschack, Manfred,Unger, Liliane,Walker, Nigel,Wernet, Wolfgang
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p. 2123 - 2128
(2007/10/03)
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