Developing an Efficient Technology for Key Intermediates Production Used in Enzymatic Synthesis of Cladribine and Nelarabine  

作　　者：Shetnev Anton Andreevich Baykov Sergey Valentinovich Smirnov Alexey Vladimirovich Dorogov Mikhail Vladimirovich Novozhilov Yury Vladimirovich 

机构地区：[1]Organic and Inorganic Chemistry Department, Ushinsky Yaroslavl State Pedagogical University, Yaroslavl 150000, Russia

出　　处：《Journal of Chemistry and Chemical Engineering》2014年第9期865-869,共5页化学与化工（英文版）

摘　　要：The pilot-scale process for preparing 2-amino-6-chloro-9-（2＇,3＇,5＇-tri-O-acetyl-Dq3-ribofuranosyl）-purine and 2-chloroadenosine has been developed with a total yield of the desired compounds 73% and 44.5%, respectively. These compounds are useful intermediates for enzymatic synthesis of active pharmaceutical ingredients Nelarabine and Cladribine. The starting material--commercially avaliable guanosine--was acetylated with acetic anhydride, yielding 2,3,5-tri-O-acetylguanosine, which was further deoxyhalogenated with phosphorous oxychloride in presence of tetraethylammonia chloride. Diazotization of the resulting intermediate with tert-butylnitrite leads to the corresponding ribofuranosyl-substituted 2,6-dichloropurine, which was converted to 6-chloroadenosine by reaction with methanolic ammonia.

关 键 词：NELARABINE CLADRIBINE pharmaceutical intermediate pilot-scale process. 

分 类 号：TQ460.4[化学工程—制药化工] TQ465.1