Invention Grant
- Patent Title: Production of highly fat-soluble phosphoramidite
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Application No.: US16958100Application Date: 2018-12-26
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Publication No.: US11891412B2Publication Date: 2024-02-06
- Inventor: Tsuyoshi Fujihara , Kenichi Nakamura , Toru Kurome , Daisuke Sasahara , Akiko Shimahara , Masahiro Neya
- Applicant: KNC LABORATORIES CO., LTD.
- Applicant Address: JP Kobe
- Assignee: KNC LABORATORIES CO., LTD.
- Current Assignee: KNC LABORATORIES CO., LTD.
- Current Assignee Address: JP Hyogo
- Agency: Hamre, Schumann, Mueller & Larson, P.C.
- Priority: JP 17252107 2017.12.27
- International Application: PCT/JP2018/047748 2018.12.26
- International Announcement: WO2019/131719A 2019.07.04
- Date entered country: 2020-09-17
- Main IPC: C07H21/04
- IPC: C07H21/04

Abstract:
The purpose of the present invention is to provide a method for purifying and preparing a highly liposoluble phosphoramidite, as well as a capping reaction using the highly liposoluble phosphoramidite compound, and as well as a method for preparing oligonucleotide by a liquid phase process using a pseudo solid phase protecting group said method comprising the capping reaction step. The present invention also provides a method for preparing a compound represented by formula (I) [wherein, R1, R2 and R3 are defined as described in the Detailed Description], which comprises the following steps: (1) reacting an aliphatic alcohol and a trivalent phosphorus compound in organic solvent in the presence of an activator or an organic base; (2) washing the resulting reaction mixture with water in a reparatory funnel; (3) recovering the organic layer after the step (2) and concentrating it (with the proviso that the organic solvent used in the step (1) is a nitrile solvent, the steps (2) to (3) may be omitted); (4) solubilizing the resulting residue obtained in the step (3) in an aliphatic hydrocarbon solvent (with the proviso that the organic solvent used in the step (1) is an aliphatic hydrocarbon solvent, the steps (2) to (3) may be omitted); (5) washing the aliphatic hydrocarbon solution prepared in the step (4) with a nitrile solvent in a separatory funnel; (6) recovering the aliphatic hydrocarbon solution after the step (5) to obtain a solution of a phosphoramidite compound. Also the present invention provides also a solution containing highly liposoluble phosphoramidite compound obtained by the preparation method, a capping reagent comprising the same solution and optionally an additive, a capping reaction using the same capping reagent, as well as a method for preparing (oligo)nucleotide by using the pseudo solid phase protecting group, said method comprising the capping reaction step.
Public/Granted literature
- US20210087220A1 PRODUCTION OF HIGHLY FAT-SOLUBLE PHOSPHORAMIDITE Public/Granted day:2021-03-25
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