CN107250100B - 制备nep抑制剂的工艺和中间体 - Google Patents

制备nep抑制剂的工艺和中间体 Download PDF

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CN107250100B
CN107250100B CN201680010250.0A CN201680010250A CN107250100B CN 107250100 B CN107250100 B CN 107250100B CN 201680010250 A CN201680010250 A CN 201680010250A CN 107250100 B CN107250100 B CN 107250100B
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alkyl
hydrogen
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CN107250100A (zh
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B·马丁
F·曼德莱利
F·文图罗尼
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Novartis AG
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/10—Preparation of nitro compounds by substitution of functional groups by nitro groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0237—Amines
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    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0241—Imines or enamines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
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    • B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
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    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
    • B01J31/0249—Ureas (R2N-C(=O)-NR2)
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0245—Nitrogen containing compounds being derivatives of carboxylic or carbonic acids
    • B01J31/0251—Guanidides (R2N-C(=NR)-NR2)
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    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0255—Phosphorus containing compounds
    • B01J31/0264—Phosphorus acid amides
    • B01J31/0265—Phosphazenes, oligomers thereof or the corresponding phosphazenium salts
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    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0255—Phosphorus containing compounds
    • B01J31/0267—Phosphines or phosphonium compounds, i.e. phosphorus bonded to at least one carbon atom, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, the other atoms bonded to phosphorus being either carbon or hydrogen
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    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/01—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms
    • C07C205/03—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
    • C07C205/04—Compounds containing nitro groups bound to a carbon skeleton having nitro groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
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    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/50—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
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    • C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
    • C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
    • C07C205/50—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C205/53—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/04—Formation of amino groups in compounds containing carboxyl groups
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    • C07—ORGANIC CHEMISTRY
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    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07C231/00—Preparation of carboxylic acid amides
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    • C07—ORGANIC CHEMISTRY
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    • C07C233/00—Carboxylic acid amides
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    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
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    • C07C335/04—Derivatives of thiourea
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    • 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
    • C07D207/06—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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
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    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
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    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/535—Organo-phosphoranes
    • C07F9/5355—Phosphoranes containing the structure P=N-
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    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
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    • C07C2601/14—The ring being saturated
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    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Catalysts (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
CN201680010250.0A 2015-02-13 2016-02-11 制备nep抑制剂的工艺和中间体 Active CN107250100B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP15155147 2015-02-13
EP15155147.0 2015-02-13
PCT/IB2016/050725 WO2016128924A1 (en) 2015-02-13 2016-02-11 Process and intermediates for the preparation of nep inhibitors

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CN107250100A CN107250100A (zh) 2017-10-13
CN107250100B true CN107250100B (zh) 2019-12-06

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US (1) US10385004B2 (OSRAM)
EP (1) EP3256444B1 (OSRAM)
JP (1) JP6665193B2 (OSRAM)
CN (1) CN107250100B (OSRAM)
TW (1) TW201632493A (OSRAM)
WO (1) WO2016128924A1 (OSRAM)

Families Citing this family (5)

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JP6945619B2 (ja) * 2016-08-17 2021-10-06 ノバルティス アーゲー Ｎｅｐ阻害剤合成のための新規な方法および中間体
AU2017371353B2 (en) * 2016-12-09 2022-02-03 Celltaxis, Llc Monamine and monoamine derivatives as inhibitors of leukotriene A4 hydrolase
CN109053800B (zh) * 2018-07-30 2020-08-14 湖北大学 季鏻盐支载手性氨基-硫脲及其制备方法和用途
CN113121342B (zh) * 2019-12-31 2022-05-31 浙江医药股份有限公司新昌制药厂 一种沙库必曲中间体的制备方法及应用
CN116987012B (zh) * 2022-04-29 2025-08-12 凯特立斯（深圳）科技有限公司 沙库必曲中间体、其制备方法及其应用

Citations (2)

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CN101952249A (zh) * 2008-01-17 2011-01-19 诺瓦提斯公司 制备5-联苯-4-基-2-甲基戊酸衍生物的方法和中间体
WO2014064466A2 (en) * 2012-10-26 2014-05-01 Isis Innovation Limited Bifunctional organic catalysts

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JPS5439029A (en) * 1977-09-01 1979-03-24 Sagami Chem Res Center Nitro compounds
US5217996A (en) 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
EP1903027A1 (en) * 2006-09-13 2008-03-26 Novartis AG Process for preparing biaryl substituted 4-amino-butyric acid or derivatives thereof and their use in the production of NEP inhibitors
SG185318A1 (en) 2007-01-12 2012-11-29 Novartis Ag Process for preparing 5-biphenyl-4-amino-2-methyl pentanoic acid
CN101774941A (zh) 2009-01-13 2010-07-14 浙江九洲药业股份有限公司 2-酰基氨基-3-联苯基丙酸的制备及拆分方法
BRPI1011657A2 (pt) * 2009-05-28 2019-04-16 Novartis Ag derivados aminopropiônicos substituídos como inibidores de neprilisina
EP2480523B1 (en) 2009-09-23 2017-03-01 Zhejiang Jiuzhou Pharmaceutical Co., Ltd. Process for manufacture of n-acylbphenyl alanine
CN104262228B (zh) 2010-01-22 2017-01-18 诺华股份有限公司 中性内肽酶抑制剂中间体和其制备方法
ES2608780T3 (es) 2010-08-23 2017-04-17 Novartis Ag Nuevo proceso para la preparación de intermediarios útiles para la elaboración de inhibidores de NEP
ES2576179T3 (es) 2010-08-23 2016-07-06 Novartis Ag Proceso para la preparación de intermediarios para la elaboración de inhibidores de NEP
AR092278A1 (es) 2012-08-31 2015-04-08 Novartis Ag Proceso de obtencion de derivados n-acilicos de bifenil-alanina e intermediarios relacionados
WO2015189862A1 (en) * 2014-06-10 2015-12-17 Council Of Scientific & Industrial Research Chiral amines, a process for preparation and use thereof

Patent Citations (2)

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Publication number Priority date Publication date Assignee Title
CN101952249A (zh) * 2008-01-17 2011-01-19 诺瓦提斯公司 制备5-联苯-4-基-2-甲基戊酸衍生物的方法和中间体
WO2014064466A2 (en) * 2012-10-26 2014-05-01 Isis Innovation Limited Bifunctional organic catalysts

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JP6665193B2 (ja) 2020-03-13
TW201632493A (zh) 2016-09-16
EP3256444B1 (en) 2019-03-27
US10385004B2 (en) 2019-08-20
EP3256444A1 (en) 2017-12-20
WO2016128924A1 (en) 2016-08-18
US20180022690A1 (en) 2018-01-25
CN107250100A (zh) 2017-10-13
JP2018506541A (ja) 2018-03-08

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