845616-83-3Relevant articles and documents
Bitopertin synthetic method and intermediate
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, (2018/03/26)
The present invention discloses a new synthesis method and intermediates of Bitopertin. According to the Bitopertin synthesis method, 5-methylsulfonyl-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]benzoic acid is adopted as a raw material, and continuous multi-step operations such as chlorination, acylation, deprotection, condensation and re-crystallization are subjected to performed to obtain the Bitopertin, wherein the intermediates in each step do not require further purification, and the total yield can achieve more than or equal to 80%.
Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF3-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation
Sieber, Joshua D.,Rodriguez, Sonia,Frutos, Rogelio,Buono, Frederic,Zhang, Yongda,Li, Ning,Qu, Bo,Premasiri, Ajith,Li, Zhibin,Han, Zhengxu S.,Xu, Yibo,Byrne, Denis,Haddad, Nizar,Lorenz, Jon,Grinberg, Nelu,Kurouski, Dmitry,Lee, Heewon,Narayanan, Bikshandarkoil,Nummy, Laurence,Mulder, Jason,Brown, Jack D.,Granger, Alice,Gao, Joe,Krawiec, Mariusz,Williams, Zeena,Pennino, Scott,Song, Jinhua J.,Hossain, Azad,Yee, Nathan K.,Busacca, Carl,Roschangar, Frank,Xin, Yanchao,Mao, Zhantong,Zhang, Xinzhu,Hong, Yaping,Senanayake, Chris H.
, p. 1448 - 1461 (2018/02/10)
A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).
Selective GlyT1 inhibitors: Discovery of [4-(3-fluoro-5- trifluoromethylpyridin-2-yl)piperazin-1-yl][5-methanesulfonyl-2-((S)-2,2, 2-trifluoro-1-methylethoxy)phenyl]methanone (RG1678), a promising novel medicine to treat schizophrenia
Pinard, Emmanuel,Alanine, Alexander,Alberati, Daniela,Bender, Markus,Borroni, Edilio,Bourdeaux, Patrick,Brom, Virginie,Burner, Serge,Fischer, Holger,Hainzl, Dominik,Halm, Remy,Hauser, Nicole,Jolidon, Synese,Lengyel, Judith,Marty, Hans-Peter,Meyer, Thierry,Moreau, Jean-Luc,Mory, Roland,Narquizian, Robert,Nettekoven, Mathias,Norcross, Roger D.,Puellmann, Bernd,Schmid, Philipp,Schmitt, Sebastien,Stalder, Henri,Wermuth, Roger,Wettstein, Joseph G.,Zimmerli, Daniel
experimental part, p. 4603 - 4614 (2010/09/17)
The GlyT1 transporter has emerged as a key novel target for the treatment of schizophrenia. Herein, we report on the optimization of the 2-alkoxy-5-methylsulfonebenzoylpiperazine class of GlyT1 inhibitors to improve hERG channel selectivity and brain penetration. This effort culminated in the discovery of compound 10a (RG1678), the first potent and selective GlyT1 inhibitor to have a beneficial effect in schizophrenic patients in a phase II clinical trial.
