745051-65-4Relevant academic research and scientific papers
Scalable synthesis of a nonracemic α-arylpropionic acid via ketene desymmetrization for a glucokinase activator
Yamagami, Takafumi,Moriyama, Noriaki,Kyuhara, Masahiro,Moroda, Atsushi,Uemura, Takeshi,Matsumae, Hiroaki,Moritani, Yasunori,Inoue, Isao
, p. 437 - 445 (2014/04/17)
Process research and development for a synthesis of the chiral carboxylic acid (R)-2 as a key intermediate of the glucokinase activator (R)-1 is described. The construction of the stereocenter at the α-carbon is a key point for the synthesis of (R)-2. The proposed process utilizes desymmetrization of a ketene in situ generated from the corresponding racemic carboxylic acid Rac-2 with (R)-pantolactone as a chiral auxiliary followed by hydrolysis of the resulting ester. This key step has been successfully scaled up to 20 kg, which demonstrates that this synthetic approach is comparable with a previously reported approach via enantioselective hydrogenation.
Development of an enantioselective hydrogenation based synthesis of a glucokinase activator
Magnus, Nicholas A.,Braden, Timothy M.,Buser, Jonas Y.,Debaillie, Amy C.,Heath, Perry C.,Ley, Christopher P.,Remacle, Jacob R.,Varie, David L.,Wilson, Thomas M.
experimental part, p. 830 - 835 (2012/08/27)
This article describes the development and optimization of chemical reactions and subsequent multikilogram preparation of the glucokinase activator (R)-1 to fund clinical evaluation as a potential therapeutic for type II diabetes. The major process developments presented here are a Wittig olefination isomerization based synthesis of an E-acrylic acid, an optimized enantioselective hydrogenation of the E-acrylic acid, and a challenging final amide coupling.
CRYSTALLINE (R)-2-(4-CYCLOPROPANESULPHONYL-PHENYL)-N-PYRAZIN-2-YL-3-(TETRAHYDROPYRAN-4-YL)-PROPIONAMIDE
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Page/Page column 4; 5-6, (2009/07/25)
Crystalline R-2-(4-cyclopropanesulfonyl-phenyl)-N-pyrazin-2-yl-3-(tetrahydropyran-4-yl)-propionamide and methods of its preparation and use are disclosed.
ENANTIOSELECTIVE PROCESS
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Page/Page column 14-15, (2008/06/13)
A process for the production of compounds comprising the enantioselective hydrogenation of 2-substituted acrylic acid derivatives.
TRI(CYCLO) SUBSTITUTED AMIDE COMPOUNDS
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Page 62, (2008/06/13)
Compounds of Formula (I): or pharmaceutically acceptable salts thereof, are useful in the prophylactic and therapeutic treatment of hyperglycemia and diabetes.
