CN103282361A - (s,s)-2,8-二氮杂双环[4,3,0]壬烷的不对称合成方法、相关原料及制备方法 - Google Patents

(s,s)-2,8-二氮杂双环[4,3,0]壬烷的不对称合成方法、相关原料及制备方法 Download PDF

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CN103282361A
CN103282361A CN2012800032463A CN201280003246A CN103282361A CN 103282361 A CN103282361 A CN 103282361A CN 2012800032463 A CN2012800032463 A CN 2012800032463A CN 201280003246 A CN201280003246 A CN 201280003246A CN 103282361 A CN103282361 A CN 103282361A
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amino protecting
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CN103282361B (zh
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申屠晓波
祁彦涛
谢凌拾
王博
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Shanghai Puyi Chemical Tech Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • 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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyrrole Compounds (AREA)

Abstract

本发明涉及莫西沙星的手性中间体(S,S)-2,8-二氮杂双环[4,3,0]壬烷(I)的不对称合成方法，式(II)所示的吡咯烷-3-酮与手性胺(R)-1-苯乙胺通过脱水反应得到亚胺或烯胺化合物，再还原所述的亚胺或烯胺化合物得到具有式(I)手性结构的式(III)或(IV)化合物，然后通过分子内关环、脱除手性辅基和氨基保护基得到式(I)化合物。本发明还涉及式(II)所示的吡咯烷-3-酮及其制备方法，
Figure DDA00003015069700011
其中，R为氨基保护基，特别是可以通过水解或氢化去除的C1-4烷氧羰基、苄氧羰基或苄基。Z=H2或O；当Z=H2时，Y为氯、溴、碘、甲磺酸酯、对甲苯磺酸酯、羟基或带保护的羟基；当Z=O时，Y为OR1，R1为C1-4烷基。

Description

PCT国内申请，说明书已公开。

Claims (1)

  1. PCT国内申请，权利要求书已公开。
CN201280003246.3A 2011-10-14 2012-09-20 (s，s)-2,8-二氮杂双环[4,3,0]壬烷的不对称合成方法、相关原料及制备方法 Active CN103282361B (zh)

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CN107686852A (zh) * 2016-08-04 2018-02-13 上海朴颐化学科技有限公司 一种莫西沙星中间体化合物的制备方法
CN108623580A (zh) * 2017-03-17 2018-10-09 北大医药股份有限公司 莫西沙星侧链及其中间体的制备方法
CN110615747A (zh) * 2018-06-20 2019-12-27 广东东阳光药业有限公司 一种二氢茚中间体的制备方法

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CN104262225B (zh) * 2014-08-24 2017-02-01 浙江新东港药业股份有限公司 一种3‑氨基吡咯烷化合物及其合成方法和用途
CN105418606B (zh) * 2015-11-24 2017-03-08 浙江省诸暨合力化学对外贸易有限公司 8‑苄基‑2,8‑二氮杂双环[4,3,0]‑壬烷的制备方法
CN107793414B (zh) * 2016-09-06 2019-07-23 上虞京新药业有限公司 (s,s)-2,8-二氮杂双环[4.3.0]壬烷的合成方法
CN108863886A (zh) * 2018-08-01 2018-11-23 江苏八巨药业有限公司 一种制备3-（3-氯丙基）-4-氧代吡咯烷-1-羧酸乙酯的方法
CN109912595B (zh) * 2019-03-29 2020-08-25 成都施贝康生物医药科技有限公司 一种抗炎药物及其用途
CN112574195B (zh) * 2019-09-30 2024-02-02 宜昌东阳光长江药业股份有限公司 一种中间体的制备方法
CN112920184B (zh) * 2021-02-06 2022-03-01 台州市生物医化产业研究院有限公司 一种制备莫西沙星中间体(s,s)-2,8-二氮杂二环[4,3,0]壬烷的方法
CN112939847B (zh) * 2021-02-06 2022-05-13 台州市生物医化产业研究院有限公司 一种制备莫西沙星中间体(s,s)-2,8-二氮杂二环[4,3,0]壬烷的方法

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CN107686852B (zh) * 2016-08-04 2022-08-02 上海朴颐化学科技有限公司 一种莫西沙星中间体化合物的制备方法
CN108623580A (zh) * 2017-03-17 2018-10-09 北大医药股份有限公司 莫西沙星侧链及其中间体的制备方法
CN110615747A (zh) * 2018-06-20 2019-12-27 广东东阳光药业有限公司 一种二氢茚中间体的制备方法

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EP2679588B1 (en) 2015-07-08
WO2013053281A1 (zh) 2013-04-18
CN103282361B (zh) 2014-12-17
JP2014504616A (ja) 2014-02-24
US20140066626A1 (en) 2014-03-06
CN103044418B (zh) 2015-02-04
US9238648B2 (en) 2016-01-19
EP2679588A4 (en) 2014-03-12
EP2679588A1 (en) 2014-01-01
JP5963778B2 (ja) 2016-08-03
ES2548078T3 (es) 2015-10-13
CN103044418A (zh) 2013-04-17

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