Large-scale synthesis of high purity "Phos reagent" useful for oligonucleotide therapeutics

被引：9

作者：

Gukathasan, R

Massoudipour, M

Gupta, I

Chowdhury, A

Pulst, S

Ratnam, S

Sanghvi, YS

Laneman, SA

机构：

[1] Digital Specialty Chem Inc, Toronto, ON M1E 4Y4, Canada

[2] Rasayan Inc, Encinitas, CA 92024 USA

来源：

JOURNAL OF ORGANOMETALLIC CHEMISTRY | 2005年 / 690卷 / 10期

关键词：

phosphoramidites; oligonucleotide; phosphitylation;

D O I：

10.1016/j.jorganchem.2004.10.014

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

A large-scale, cost-effective, and environmentally clean synthesis of high purity 2-cyanoethyl-N,N,N',N'-tetraisopropylphosphorodiamidite (Phos reagent) has been accomplished on a commercial scale. Treatment of PCl3 with diisopropylamine followed by 3-hydroxylpropionitrile furnished the Phos reagent in excellent yield. The P-31 NMR of the Phos reagent prepared at large-scale show consistent purities > 99% when several key factors are controlled. These controlling factors include sourcing high purity key raw materials, identification and elimination of critical impurities, stability and storage of Phos reagent. (c) 2004 Elsevier B.V. All rights reserved.

引用

页码：2603 / 2607

页数：5

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