68843-73-2Relevant articles and documents
Dynamic kinetic resolution synthesis method for key intermediate of new osteoporotic drug Odankati
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Paragraph 0047; 0048, (2018/10/19)
The invention discloses a dynamic kinetic resolution synthesis method for a key intermediate of a new osteoporotic drug Odankati. The method comprises the following steps: synthesizing 2-amino-4-methylvalerate from 2-diphenylmethylketimino ethyl acetate and 3-chloro-2-methylpropylene; by taking salicylaldehyde and carbonyl compounds as catalysts, and chiral tartaric acid or camphor sulfonic acid as a chiral source, carrying out dynamic kinetic resolution, so as to synthesize an Odankati key intermediate (S) (or (R))-4-methyl-4-ene 2-pentanoic acid ethyl ester. By adopting the method, aldehydeand carbonyl compounds which are cheap and easy to obtain are adopted as catalysts, the camphor sulfonic acid is adopted as the chiral source, and the reagents and catalysts are cheap and easy to obtain, so that the preparation cost of the key intermediate can be greatly reduced, and good economy can be achieved; the synthesis method disclosed by the invention is simple to operate, gentle in reaction condition, good in reaction property, good in reaction selectivity, high in yield, easy in product purification and very small in environment pollution.
Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: A potential therapeutic agent for the treatment of hepatitis C infection
Venkatraman, Srikanth,Bogen, Stéphane L.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin,Jao, Edwin,Liu, Yi-Tsung,Lovey, Raymond,Hendrata, Siska,Huang, Yuhua,Pan, Weidong,Parekh, Tejal,Pinto, Patrick,Popov, Veljko,Pike, Russel,Ruan, Sumei,Santhanam, Bama,Vibulbhan, Bancha,Wu, Wanli,Yang, Weiying,Kong, Jianshe,Liang, Xiang,Wong, Jesse,Liu, Rong,Butkiewicz, Nancy,Chase, Robert,Hart, Andrea,Agrawal, Sony,Ingravallo, Paul,Pichardo, John,Kong, Rong,Baroudy, Bahige,Malcolm, Bruce,Guo, Zhuyan,Prongay, Andrew,Madison, Vincent,Broske, Lisa,Cui, Xiaoming,Cheng, Kuo-Chi,Hsieh, Yunsheng,Brisson, Jean-Marc,Prelusky, Danial,Korfmacher, Walter,White, Ronald,Bogdanowich-Knipp, Susan,Pavlovsky, Anastasia,Bradley, Prudence,Saksena, Anil K.,Ganguly, Ashit,Piwinski, John,Girijavallabhan, Viyyoor,Njoroge, F. George
, p. 6074 - 6086 (2007/10/03)
Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or polyethylene glycol (PEG)-interferon-α alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
SYNTHESIS OF α-AMINOACIDS BY CATALYTIC PALLADIUM (O) ALKYLATION OF BASES
Ferroud, D.,Genet, J. P.,Kiolle, R.
, p. 23 - 26 (2007/10/02)
Schiff bases 1 b, 1 c, 2 derived from glycine ester or aminoacetonitrile were alkylated with allylic acetates 3 a, 3 b or allylic carbonates 3 c, 3 d, 4 a, 4 b (under neutral conditions) in presence of catalytic amount of palladium (O).After hydrolysis higher and functionalized α-aminoesters were obtained in good yields (50 to 85 percent).
