CN103443115A - 制备齐多夫定及其中间体的方法 - Google Patents

制备齐多夫定及其中间体的方法 Download PDF

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Publication number
CN103443115A
CN103443115A CN2011800025200A CN201180002520A CN103443115A CN 103443115 A CN103443115 A CN 103443115A CN 2011800025200 A CN2011800025200 A CN 2011800025200A CN 201180002520 A CN201180002520 A CN 201180002520A CN 103443115 A CN103443115 A CN 103443115A
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China
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reaction
solvent
sodium
formula
reaction temperature
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CN103443115B (zh
Inventor
李金亮
赵楠
刘澍
程风华
熊玉友
周春峰
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Jiangsu Puxin Pharmaceutical Co ltd
Jiangxi Desino Pharmaceutical Co ltd
Shanghai Desano Pharmaceuticals Investment Co ltd
Shanghai Desano Chemical Pharmaceutical Co Ltd
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Jiangsu Puxin Pharmaceuticals Dev Co ltd
Shanghai Desano Pharmaceutical Investment Co ltd
Shanghai Desano Chemical Pharmaceutical Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/06—Pyrimidine radicals
    • C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Saccharide Compounds (AREA)

Abstract

本发明涉及一种制备齐多夫定(B)的方法，所述方法包括如下步骤：1）以2’-卤代胸苷(A)为原料，将其5’-位羟基进行保护，得到式（I）化合物；2）式（I）化合物脱卤得到式（II）化合物；3）式（II）化合物经3’-位羟基酰化保护得到式（III）化合物；4）式（III）化合物进行消除反应得到式（IV）化合物；5）式（IV）化合物经叠氮化反应得到式（V）化合物；6）式（V）化合物脱保护得到齐多夫定(B)；上述路线的反应式如(C)。式中，X为卤素；P1为羟基保护基；P2为C1-4烷基磺酰基、氟代的C1-4烷基磺酰基、芳基磺酰基或-CS-R，其中R为C1-4烷基。本发明还涉及通式(I)的中间体，其中X和P1的定义如上所述。

Description

PCT国内申请，说明书已公开。

Claims (12)

  1. PCT国内申请，权利要求书已公开。
CN201180002520.0A 2011-11-07 2011-11-07 制备齐多夫定及其中间体的方法 Active CN103443115B (zh)

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PCT/CN2011/081853 WO2013067664A1 (zh) 2011-11-07 2011-11-07 制备齐多夫定及其中间体的方法

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CN103443115A true CN103443115A (zh) 2013-12-11
CN103443115B CN103443115B (zh) 2015-09-23

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Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104844672A (zh) * 2015-04-09 2015-08-19 苏州华诺医药有限公司 制备齐多夫定及其中间体的方法
CN113461759A (zh) * 2021-07-02 2021-10-01 华东理工大学 基于连续流微反应技术合成齐多夫定叠氮化中间体的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0292101A2 (en) * 1987-03-25 1988-11-23 The Wellcome Foundation Limited Process for the preparation of 3'-azido-3'-deoxythymidine and intermediates
EP0638586A2 (en) * 1993-08-04 1995-02-15 Ajinomoto Co., Inc. Nucleoside derivatives and methods for producing them
CN1216766A (zh) * 1998-10-06 1999-05-19 中国人民解放军第二军医大学 一种β-胸苷的制备方法
CN1453287A (zh) * 2002-04-25 2003-11-05 北京万全阳光医药科技有限公司 “一锅法”制备2，3`－脱水－5`－o－(特戊酰基)胸腺嘧啶脱氧核苷及其衍生物(氧桥物)的新方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0292101A2 (en) * 1987-03-25 1988-11-23 The Wellcome Foundation Limited Process for the preparation of 3'-azido-3'-deoxythymidine and intermediates
EP0638586A2 (en) * 1993-08-04 1995-02-15 Ajinomoto Co., Inc. Nucleoside derivatives and methods for producing them
CN1216766A (zh) * 1998-10-06 1999-05-19 中国人民解放军第二军医大学 一种β-胸苷的制备方法
CN1453287A (zh) * 2002-04-25 2003-11-05 北京万全阳光医药科技有限公司 “一锅法”制备2，3`－脱水－5`－o－(特戊酰基)胸腺嘧啶脱氧核苷及其衍生物(氧桥物)的新方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
GEORGY V SIDOROV，等: "The synthesis of some tritium-labeled terminators of DNA synthesis", 《JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS》 *
NAVEEN C. SRIVASTAV，等: "Antiviral Activity of Various 1-(2’-Deoxy-β-D-lyxofuranosyl)，1-(2’-Fluoro-β-D-xylofuranosyl)，1-(3’-Fluoro-β-D-arabinofuranosyl)，and 2’-Fluoro-2’，3’-didehydro-2’，3’-dideoxyribose Pyrimidine Nucleoside Analogues against Duck", 《J. MED. CHEM.》 *
刘世领，等: "齐多夫定的合成", 《中国医药工业杂志》 *

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CN103443115B (zh) 2015-09-23

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Address after: No. 1479, zhangheng Road, Pudong New Area, Shanghai, 201203

Patentee after: SHANGHAI DESANO PHARMACEUTICALS INVESTMENT Co.,Ltd.

Patentee after: SHANGHAI DESANO CHEMICAL PHARMACEUTICAL Co.,Ltd.

Patentee after: JIANGSU PUXIN PHARMACEUTICAL Co.,Ltd.

Address before: No. 1479, zhangheng Road, Pudong New Area, Shanghai, 201203

Patentee before: SHANGHAI DESANO PHARMACEUTICALS INVESTMENT Co.,Ltd.

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Effective date of registration: 20211223

Address after: 331299 Zhangshu salt chemical industrial base, Yichun City, Jiangxi Province

Patentee after: Jiangxi desino Pharmaceutical Co.,Ltd.

Patentee after: SHANGHAI DESANO PHARMACEUTICALS INVESTMENT Co.,Ltd.

Address before: No. 1479, zhangheng Road, Pudong New Area, Shanghai, 201203

Patentee before: SHANGHAI DESANO PHARMACEUTICALS INVESTMENT Co.,Ltd.

Patentee before: SHANGHAI DESANO CHEMICAL PHARMACEUTICAL Co.,Ltd.

Patentee before: JIANGSU PUXIN PHARMACEUTICAL Co.,Ltd.

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