WO2023109968A3 - 非奈利酮及其中间体的合成方法 - Google Patents

非奈利酮及其中间体的合成方法 Download PDF

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WO2023109968A3
WO2023109968A3 PCT/CN2022/139823 CN2022139823W WO2023109968A3 WO 2023109968 A3 WO2023109968 A3 WO 2023109968A3 CN 2022139823 W CN2022139823 W CN 2022139823W WO 2023109968 A3 WO2023109968 A3 WO 2023109968A3
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compound
solvent
acid
finerenone
reduced
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PCT/CN2022/139823
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English (en)
French (fr)
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WO2023109968A2 (zh
Inventor
阮诗文
张薇
严恭超
张鑫鑫
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上海鼎雅药物化学科技有限公司
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Publication of WO2023109968A2 publication Critical patent/WO2023109968A2/zh
Publication of WO2023109968A3 publication Critical patent/WO2023109968A3/zh

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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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明提供了一种新的非奈利酮中间体的合成方法。该方法包括：(1)在酸存在下，并在惰性溶剂或无溶剂条件中，由丙二酸二乙酯、4-氰基-2-甲氧基苯甲醛、4-氨基-5-甲基-2-羟基吡啶反应制备得到化合物1；(2)步骤(1)得到的化合物1在惰性溶剂或无溶剂条件中，酸催化下与原甲酸三乙酯发生烷基化反应制备得到化合物2；(3)将步骤(2)得到的化合物2经还原剂还原制备得到化合物3；(4)在催化剂存在下，化合物3和醇经化学方法拆分，制备得到手性化合物4；反应式如下所示：应用本发明的技术方案，避免使用手性柱拆分方法，降低了成本；所采用化学方法拆分，降低了原料损耗，后处理简单，利于工业化放大生产。
PCT/CN2022/139823 2021-12-18 2022-12-18 非奈利酮及其中间体的合成方法 WO2023109968A2 (zh)

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CN202111555792.5A CN114149427A (zh) 2021-12-18 2021-12-18 非奈利酮及其中间体的合成方法
CN202111555792.5 2021-12-18

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CN114149427A (zh) * 2021-12-18 2022-03-08 上海鼎雅药物化学科技有限公司 非奈利酮及其中间体的合成方法
CN114524812A (zh) * 2022-03-18 2022-05-24 湖南凯铂生物药业有限公司 1,4-二氢-1,6-萘啶化合物的晶型制备以及合成方法
CN115322194B (zh) * 2022-08-23 2024-04-09 浙江国邦药业有限公司 一种非奈利酮中间体羧酸拆分方法

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