RU2617696C2 - Способы и соединения, которые можно использовать для синтеза антагонистов рецепторов орексина-2 - Google Patents

Способы и соединения, которые можно использовать для синтеза антагонистов рецепторов орексина-2 Download PDF

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RU2617696C2
RU2617696C2 RU2014137470A RU2014137470A RU2617696C2 RU 2617696 C2 RU2617696 C2 RU 2617696C2 RU 2014137470 A RU2014137470 A RU 2014137470A RU 2014137470 A RU2014137470 A RU 2014137470A RU 2617696 C2 RU2617696 C2 RU 2617696C2
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compound
formula
alkyl
group
halogen
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RU2014137470A
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RU2014137470A (ru
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Джордж Энтони МОНИЗ
Энни Жу УИЛКОКСЕН
Фарид БЕНАЙУД
Дзаемоон ЛИ
Хоймин ЧЖАН
Таро ТЕРАУТИ
Аюми ТАКЕМУРА
Ю Йосида
Тосиаки ТАНАКА
Кеиити СОРИМАТИ
Йосимицу НАОЕ
Юдзи КАДЗУТА
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ЭЙСАЙ Ар ЭНД Ди МЕНЕДЖМЕНТ КО., ЛТД
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/42—Separation; Purification; Stabilisation; Use of additives
    • C07C303/44—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/63—Esters of sulfonic acids
    • C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
    • C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C07C309/66—Methanesulfonates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C07C69/16—Acetic acid esters of dihydroxylic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
    • C12P7/22—Preparation of oxygen-containing organic compounds containing a hydroxy group aromatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
    • C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
    • C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
    • C07C33/36—Polyhydroxylic alcohols containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/03—Preparation of carboxylic acid esters by reacting an ester group with a hydroxy group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
    • C07D307/83—Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Furan Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
RU2014137470A 2012-02-17 2013-02-14 Способы и соединения, которые можно использовать для синтеза антагонистов рецепторов орексина-2 RU2617696C2 (ru)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261600109P 2012-02-17 2012-02-17
US61/600,109 2012-02-17
PCT/US2013/026204 WO2013123240A1 (en) 2012-02-17 2013-02-14 Methods and compounds useful in the synthesis of orexin-2 receptor antagonists

Publications (2)

Publication Number Publication Date
RU2014137470A RU2014137470A (ru) 2016-04-10
RU2617696C2 true RU2617696C2 (ru) 2017-04-26

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Country Link
US (3) US9416109B2 (enExample)
EP (1) EP2814798B1 (enExample)
JP (1) JP6147279B2 (enExample)
CN (1) CN104114524B (enExample)
BR (1) BR112014019909B1 (enExample)
CA (1) CA2861493C (enExample)
ES (1) ES2733750T3 (enExample)
HU (1) HUE043995T2 (enExample)
IL (1) IL232949A (enExample)
MX (1) MX352881B (enExample)
RU (1) RU2617696C2 (enExample)
SG (1) SG11201403216UA (enExample)
WO (1) WO2013123240A1 (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2823998C2 (ru) * 2019-05-15 2024-07-31 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Способ и соединение, пригодные в получении антагониста рецептора орексина-2, и лемборексант, содержащий небольшое количество примесей
US12479819B2 (en) 2019-05-15 2025-11-25 Eisai R&D Management Co., Ltd. Method and compound useful in preparation of orexin-2 receptor antagonist, and lemborexant having few impurities

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US9440982B2 (en) 2012-02-07 2016-09-13 Eolas Therapeutics, Inc. Substituted prolines/piperidines as orexin receptor antagonists
JP6346862B2 (ja) 2012-02-07 2018-06-20 エオラス セラピューティクス, インコーポレイテッド オレキシンレセプターアンタゴニストとしての置換プロリン/ピペリジン
US9416109B2 (en) * 2012-02-17 2016-08-16 Eisai R&D Management Co., Ltd. Methods and compounds useful in the synthesis of orexin-2 receptor antagonists
ES2731648T3 (es) 2014-08-06 2019-11-18 Eisai R&D Man Co Ltd Método para producir un compuesto de pirimidina-1-ol y compuesto intermedio del mismo
TW201613902A (en) 2014-08-13 2016-04-16 Eolas Therapeutics Inc Difluoropyrrolidines as orexin receptor modulators
US10894789B2 (en) 2016-02-12 2021-01-19 Astrazeneca Ab Halo-substituted piperidines as orexin receptor modulators
JP7179049B2 (ja) * 2017-08-01 2022-11-28 ベルゲン ファーマシューティカル、 エルエルシー オレキシン受容体拮抗薬の結晶形及びその製造方法並びに用途
GB201807898D0 (en) * 2018-05-15 2018-06-27 Kancera Ab New processes and products with increased chiral purity
SG11202101818XA (en) * 2018-09-07 2021-03-30 Sumitomo Chemical Co Method for manufacturing cyclopropane compound
JP7281564B2 (ja) 2019-06-12 2023-05-25 ヌーリオン ケミカルズ インターナショナル ベスローテン フェノーツハップ 過酸化ジアシルを生成するためのプロセス
JP7281563B2 (ja) 2019-06-12 2023-05-25 ヌーリオン ケミカルズ インターナショナル ベスローテン フェノーツハップ ペルオキシエステルを生成するためのプロセス
US11976035B2 (en) 2019-06-12 2024-05-07 Nouryon Chemicals International B.V. Process for the production of diacyl peroxides
ES2963356T3 (es) * 2019-06-12 2024-03-26 Nouryon Chemicals Int Bv Método para aislar ácido carboxílico a partir de una corriente lateral acuosa
JP7335362B2 (ja) 2019-06-12 2023-08-29 ヌーリオン ケミカルズ インターナショナル ベスローテン フェノーツハップ 過酸化ジアシルを生成するためのプロセス
WO2020263253A1 (en) * 2019-06-26 2020-12-30 Moline Margaret Lemborexant for treating sleep issues
JP2023506025A (ja) 2019-12-11 2023-02-14 テバ チェコ インダストリーズ エス.アール.オー. レンボレキサントの固体形態
EP4076463A1 (en) 2019-12-20 2022-10-26 Eisai R&D Management Co., Ltd. Use of lemborexant for treating insomnia
IL328515A (en) 2020-01-16 2026-07-01 Eisai R&D Man Co Ltd Lamborxant drug substance and medical preparation containing it
ES2933074B2 (es) * 2021-07-26 2023-09-29 Moehs Iberica Sl Procedimiento de sintesis de 2,4-dimetilpirimidin-5-ol, nuevos intermedios de dicho procedimiento y uso del producto en la sintesis de lemborexant
WO2023178702A1 (zh) * 2022-03-25 2023-09-28 浙江华海药业股份有限公司 莱博雷生及其中间体化合物的制备方法
CN118871427A (zh) * 2022-03-25 2024-10-29 浙江华海药业股份有限公司 一种莱博雷生及其中间体的制备方法
CN114778745B (zh) * 2022-06-21 2022-09-16 南京威凯尔生物医药科技有限公司 一种高效液相色谱法检测仑布雷生中间体及其对映体杂质的方法
CN121045084A (zh) * 2024-06-01 2025-12-02 常州市第四制药厂有限公司 一种莱博雷生关键中间体及其合成方法
CN119930526B (zh) * 2025-04-07 2025-07-08 东北制药集团股份有限公司 一种莱博雷生中间体的制备方法

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RU2009147733A (ru) * 2007-05-23 2011-06-27 Мерк Шарп Энд Домэ Корп. (Us) Пиридилпиперидновые антагонисты рецептора орексинов

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2823998C2 (ru) * 2019-05-15 2024-07-31 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Способ и соединение, пригодные в получении антагониста рецептора орексина-2, и лемборексант, содержащий небольшое количество примесей
US12479819B2 (en) 2019-05-15 2025-11-25 Eisai R&D Management Co., Ltd. Method and compound useful in preparation of orexin-2 receptor antagonist, and lemborexant having few impurities

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Publication number Publication date
US20160318858A1 (en) 2016-11-03
WO2013123240A1 (en) 2013-08-22
CN104114524B (zh) 2016-08-17
US9828336B2 (en) 2017-11-28
BR112014019909A2 (enExample) 2017-06-20
EP2814798A1 (en) 2014-12-24
MX352881B (es) 2017-12-13
IL232949A0 (en) 2014-08-03
BR112014019909B1 (pt) 2020-01-28
BR112014019909A8 (pt) 2017-07-11
SG11201403216UA (en) 2014-12-30
HUE043995T2 (hu) 2019-09-30
US9416109B2 (en) 2016-08-16
US20180044285A1 (en) 2018-02-15
EP2814798B1 (en) 2019-04-03
JP6147279B2 (ja) 2017-06-14
CN104114524A (zh) 2014-10-22
CA2861493C (en) 2019-09-24
RU2014137470A (ru) 2016-04-10
JP2015509939A (ja) 2015-04-02
ES2733750T3 (es) 2019-12-02
IL232949A (en) 2016-08-31
MX2014009917A (es) 2014-11-13
CA2861493A1 (en) 2013-08-22
US20150025237A1 (en) 2015-01-22

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