An efficient four step process for the preparation of 5'-O-(4,4'-dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)-guanosine 1 was developed. Direct 2'-O-alkylation of 2,6-diaminopurine riboside 2 was accomplished via inexpensive and commercially available reagents such as KOH, DMSO and alkyl halides at room temperature in 4-6 hrs. Pure 2'-O-(2-methoxyethyl)-DAPR 3 was isolated by crystallization from methanol. Enzymatic deamination of 3 followed by selective N2-isobutyrylation and 5'-O-dimethoxytritylation furnished desired 1 in high yield and purity. Fully optimized four step synthetic process has been scaled up to the pilot plant level.

中文翻译：

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合成5'-O-（4,4'-二甲氧基三苯甲基）-N2-异丁酰基-2'-O-（2-甲氧基乙基）-鸟苷的方法开发-一种改进的第二代反义寡核苷酸的前体2'-O-烷基-2,6-二氨基嘌呤核糖苷的制备方法。

开发了一种高效的四步法，用于制备5'-O-（4,4'-二甲氧基三苯甲基）-N2-异丁酰基-2'-O-（2-甲氧基乙基）-鸟苷1。2，6-二氨基嘌呤核糖苷2的直接2'-O-烷基化反应是通过廉价且可商购的试剂（例如KOH，DMSO和烷基卤化物）在室温下于4-6小时内完成的。通过从甲醇中结晶分离出纯的2'-O-（2-甲氧基乙基）-DAPR 3。3的酶促脱氨基反应，然后进行选择性的N2-异丁酰化和5'-O-二甲氧基三苯甲基化，以高收率和纯度提供了所需的1。完全优化的四步合成工艺已扩大到试点工厂水平。