1103738-29-9Relevant articles and documents
Palladium-Catalyzed Reaction of Aryl Iodides and Glycal Enones: Application in the Preparation of Dapagliflozin Analogues
Kandasamy, Jeyakumar,Kumar Kanaujiya, Vimlesh,Kumar Singh, Adesh,Tiwari, Varsha,Venkatesh, Rapelly
, (2022/03/07)
An efficient approach for the preparation of C-1 aryl enones from aryl iodides and glycal enones by palladium-catalyzed cross-coupling reactions under ligand-free conditions was developed. A wide range of aryl iodides bearing electron-donating and withdrawing groups underwent oxidative C-1 arylation with galactal, glucal and rhamnal enones in the presence of Pd(OAc)2 and AgNO3 under mild conditions. The protecting groups, including benzyl, acetyl, pivaloyl, and benzoyl groups, were found to be compatible under standard reaction conditions. The developed methodology was applied for the preparation of dapagliflozin analogues (SGLT-2 inhibitors). Regioselective nitration of C-1 aryl enones provides C-2 nitro aryl enones in good yields.
Process development of sotagliflozin, a dual inhibitor of sodium- Glucose cotransporter-1/2 for the treatment of diabetes
Zhao, Matthew M.,Zhang, Haiming,Iimura, Shinya,Bednarz, Mark S.,Song, Qiu-Ling,Lim, Ngiap-Kie,Yan, Jie,Wu, Wenxue,Dai, Kuangchu,Gu, Xiaodong,Wang, Youchu
, p. 2689 - 2701 (2020/11/03)
The development of an efficient manufacturing process for sotagliflozin (LX4211), a dual inhibitor of sodium- glucose cotransporter-1/2 (SGLT-1/2) for the treatment of diabetes, is described. Sotagliflozin features five contiguous chiral centers on the carbohydrate core flanked by a thioether group and a biaryl moiety. Three chiral centers are obtained from the starting material L-xylose, while the other two were established (or modified) via three highly stereoselective transformations: Luche reduction (dr: 97/3), dynamic kinetic resolution of anomeric hemiacetal (dr: 95/5), and Lewis acid-promoted thiolation (dr: 1000/ 1). Global deprotection of the resulting penultimate intermediate with catalytic sodium methoxide followed by recrystallization furnishes sotagliflozin. The longest linear sequence consists of 10 steps from L-xylose with an overall yield of 40%. This process has been performed on multi-hundred kilogram batches to satisfy the drug substance development demands.
Synthetic method of 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene
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Paragraph 0028-0045; 0046-0051, (2019/02/04)
The invention belongs to the field of pharmaceutical synthesis and discloses a synthetic method of 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene. The synthetic method comprises the following steps: (S1) dissolving 4-bromobenzene ether into a solvent, adding magnesium, and reacting under the catalysis of iodine, so as to obtain a Grignard reagent; and (S2) dissolving 2-(bromomethyl)-4-iodochlorobenzeneinto the solvent, adding the Grignard reagent prepared in the step S1, and reacting under the catalysis of cuprous iodide, so as to obtain 1-chloro-2-(4-ethoxybenzyl)-4-iodobenzene. The method is short in synthetic route, the final product purity reaches up to 99.5%, and the yield reaches up to 95.9%, so that the method is beneficial to the industrialization production.