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%, respec...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.展开更多
文摘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.
