848819-60-3Relevant articles and documents
PROTEIN SECRETION INHIBITORS
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Paragraph 00205, (2022/03/09)
Provided herein are secretion inhibitors, such as inhibitors of Sec61 for example of Formula (I), methods for their preparation, related pharmaceutical compositions, and method for using the same.
Efficient and Scalable Synthesis of Glucokinase Activator with a Chiral Thiophenyl-Pyrrolidine Scaffold
Fujieda, Hiroki,Maeda, Koji,Kato, Noriyasu
, p. 69 - 77 (2019/01/24)
Herein we describe the practical synthesis of a potent glucokinase activator (1) that has a chiral thiophenyl-pyrrolidine scaffold. The key to the successful synthesis was the application of a telescoped chiral-pool synthesis from a commercially available l-proline methyl ester derivative to introduce the chirality of the thiophenyl-pyrrolidine moiety. This second-generation synthesis of 1 provided several advantages over the previous method including an operational simplicity and avoidance of purification by column chromatography. The industrial relevance of this synthetic method in large-scale preparation was demonstrated by the production of 54.6 kg of 1 with an excellent chemical and optical purity.
Continuous flow synthesis of α-halo ketones: Essential building blocks of antiretroviral agents
Pinho, Vagner D.,Gutmann, Bernhard,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.,Kappe, C. Oliver
, p. 1555 - 1562 (2014/03/21)
The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).