- Synthesis method of 2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid
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The invention relates to a synthetic method of 2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid. The invention relates to a preparation method of an ambrisentan key intermediate 2-hydroxy-3-methoxy-3,3-diphenyl propionic acid. According to the preparation
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Paragraph 0029-0031; 0035-0037; 0041-0043
(2020/05/14)
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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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Paragraph 0030; 0031; 0032; 0033; 0034; 0035; 0036
(2019/05/04)
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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; 0039
(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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Paragraph 0092; 0093
(2017/02/28)
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- LC-MS/MS characterization of forced degradation products of ambrisentan: Development and validation of a stability-indicating RP-HPLC method
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The current study reports the characterization of degradation products of ambrisentan by liquid chromatography-tandem mass spectrometry, and development and validation of a stability-indicating reversed phase high performance liquid chromatographic method
- Ramisetti, Nageswara Rao,Kuntamukkala, Ramakrishna
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p. 3050 - 3061
(2014/07/07)
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- IMPROVED PROCESS TO PREPARE S-2-HYDROXY-3-METHOXY-3,3-DIPHENYL PROPIONIC ACID
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Disclosed is a process for the preparation of S-2-Hydroxy-3-methoxy-3,3-diphenylpropionic acid (I) the key intermediate for the preparation of Ambrisentan [(+)-2(S)-(4,6-Dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropionic acid]. Ambrisentan of the formula (IA) is approved under the trademark "Letairis " by the US Food and Drug Administration for the treatment of Pulmonary artery hypertension(PAH).
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Page/Page column 10
(2012/02/15)
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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 18
(2010/08/05)
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- SELECTIVE ENDOTHELIN TYPE-A ANTAGONISTS
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This invention relates to novel endothelin receptor antagonists that selectively inhibit the interaction between Endothelin-1 (ET-1) and endothelin type-A receptors, their derivatives, acceptable acid addition salts. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by endothelin receptor antagonists, particularly those diseases and conditions that are beneficially treated by selective inhibitors of endothelin type-A receptors.
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Page/Page column 24-25
(2008/12/08)
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- Structural similarity and its surprises: Endothelin receptor antagonists -process research and development report
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Process research and pilot plant processes are described for three endothelin (ET) receptor antagonists. The efficient synthesis of the parent compound Darusentan proceeds via a Darzens reaction from chloroacetate with benzophenone, addition of methanol to the resulting epoxide, saponification of the alkyl propionate and optical resolution of the racemic acid by crystallisation with a chiral amine. The final stage of the synthetic sequence involves the introduction of a pyrimidine moiety. Intermediates formed during this process can be used as starting materials for the synthesis of the two other ET receptor antagonists BSF 420627 and BSF 302146. An ether exchange reaction, which replaces the methoxy with a phenethyloxy substituent, enabled BSF 420627 to be prepared. The synthetic route to BSF 302146 employs trimethylaluminum to methylate the epoxide produced by the Darzens reaction.
- Jansen,Knopp,Amberg,Bernard,Koser,Mueller,Muenster,Pfeiffer,Riechers
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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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- Metal Exchange between an Electrogenerated Organonickel Species and Zinc Halide: Application to an Electrochemical, Nickel-Catalyzed Reformatsky Reaction
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The mechanism of the electroreductive coupling of α-chloro esters or α-chloro nitriles with carbonyl compounds by the means of a sacrificial zinc anode and a nickel catalyst was elucidated by electroanalytical techniques.The mechanism involved reduction of a Ni(II) complex to a Ni(0) complex, oxidative addition of the α-chloro ester to the Ni(0) complex, and a Zn(II)/Ni(II) exchange, leading to an organozinc Reformatsky reagent.The electrosynthesis of various β-hydroxy esters, β-hydroxy nitriles, and 2,3-epoxy esters was successfully achieved under extremely mild conditions.
- Conan, Annie,Sibille, Soline,Perichon, Jacques
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p. 2018 - 2024
(2007/10/02)
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- Dianions Derived from α-Halo Acids. The Darzens Condensation Revisited
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The dianions of α-halo carboxylic acids are readily generated by the addition of the acids to 2 equiv of lithium diisopropylamide at low temperatures.When the mixture warms to room temperature dimeric products are formed.When aldehydes and ketones were added to the cooled solutions of the dianions and the reaction mixtures were allowed to warm to room temperature, followed by acid quench, glycidic acids were formed.The glycidic acids, per se, were often too unstable to be isolated and purified but could be analyzed by conversion to their methyl esters withdiazomethane.When the reactions were quenched prematurely, α-chloro-β-hydroxy carboxylic acids were isolated.Homologated aldehydes and ketones were obtained from the glycidic acids by catalytic and thermal decarboxylation methods.
- Johnson, Carl R.,Bade, Thomas R.
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p. 1205 - 1212
(2007/10/02)
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