WO2017023124A1 - Nouveau procédé de préparation d'un dérivé de chromanol - Google Patents

Nouveau procédé de préparation d'un dérivé de chromanol Download PDF

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Publication number
WO2017023124A1
WO2017023124A1 PCT/KR2016/008580 KR2016008580W WO2017023124A1 WO 2017023124 A1 WO2017023124 A1 WO 2017023124A1 KR 2016008580 W KR2016008580 W KR 2016008580W WO 2017023124 A1 WO2017023124 A1 WO 2017023124A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound represented
preparing
represented
catalyst
Prior art date
Application number
PCT/KR2016/008580
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English (en)
Korean (ko)
Inventor
김은선
고동현
권재홍
김영주
이성아
최광도
허승평
이지윤
Original Assignee
씨제이헬스케어 주식회사
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 씨제이헬스케어 주식회사 filed Critical 씨제이헬스케어 주식회사
Priority to JP2018505683A priority Critical patent/JP6676146B2/ja
Priority to CN201680044642.9A priority patent/CN107849003A/zh
Publication of WO2017023124A1 publication Critical patent/WO2017023124A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/46—Ruthenium, rhodium, osmium or iridium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System

Definitions

  • the present invention relates to a novel process for preparing chromamanol derivatives having optical activity.
  • Chiral chromanol (chromanol) derivative compound is a substance having a variety of activities in medicine and chemistry, and there are many chiral chromanol structural compounds in the currently developed medicines.
  • the drug efficacy is often very different depending on the three-dimensional conformation. Therefore, stereoselective synthesis of chiral chromanol derivative compounds is of great importance in medicinal and organic synthesis.
  • many methods for easily synthesizing chiral chromanol derivative compounds have not been reported.
  • the present invention shows a high optical purity, does not require a separate purification process, and provides a method for producing a chromamanol derivative having an excellent production yield without using a dangerous reagent in the production process.
  • It provides a method for producing a compound represented by the formula (I) comprising the step of preparing a compound represented by the formula (I) by chiral reduction reaction of the compound represented by the formula (II) under a catalyst represented by the formula (III) or (IV).
  • * represents a Chiral center
  • the preparation method of the present invention exhibits high optical purity, which does not require a separate purification process, does not include harsh reaction conditions, and does not use dangerous reagents. It is advantageous for mass production and has a good production yield.
  • the preparing of the compound represented by Chemical Formula I is a chiral reduction reaction using the catalyst of Chemical Formula III or 4, wherein the compound represented by Chemical Formula II and the hydrogen donor are represented by Chemical Formula III or Chemical IV.
  • the reaction is carried out under a catalyst to prepare a compound represented by the above formula (I) having selectively optical activity.
  • reaction molar ratio of the compound represented by Formula II and the catalyst represented by Formula III or Formula IV may be 1: 0.0001 to 1: 0.1, preferably 0.005 to 0.001.
  • the reaction solvent in the step of preparing the compound represented by the formula (I) may be used an organic solvent widely used in the industry.
  • Halogenated hydrocarbons such as, but not limited to, dichloromethane, chloroform, 1,2-dichloroethane; Ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane; Aromatic hydrocarbons such as benzene, toluene and nitrobenzene; Sulfoxides such as dimethyl sulfoxide; Formic acid amide, such as dimethylformamide; Alcohols such as methanol, ethanol, 2-propanol and butanol; Or a mixed solvent thereof.
  • the reaction solvent in the step of preparing the compound represented by the formula (I) may be preferably a non-polar organic solvent widely used in the industry, more preferably, may be tetrahydrofuran.
  • the hydrogen donor of the present invention may be selected from formic acid, metal salts of formic acid, ammonium salts of formic acid, and mixtures of formic acid and amines.
  • the hydrogen donor may be a mixture of formic acid and amine, more preferably triethylamine (TEA) and formic acid, or diisopropylethylamine (DIPEA) and formic acid.
  • TEA triethylamine
  • DIPEA diisopropylethylamine
  • the chiral reduction reaction of the compound represented by Chemical Formula II or Chemical Formula IV may be performed at 25 ° C. to 80 ° C., preferably at 30 ° C. to 50 ° C. have.
  • a lower temperature is unsuitable for commercial production because the reaction time is too long, and a high temperature results in too low chiral purity.
  • the preparing of the compound represented by Chemical Formula I may further include performing crystallization with a crystallization solvent.
  • the crystallization solvent is for the crystallization of the compound, hexane, aliphatic hydrocarbons, C 6 ⁇ 7, such as heptane; Ethers such as diethyl ether and diisopropyl ether; Or mixed solvents thereof may be used.
  • hexane it may be used aliphatic hydrocarbons, C 6 ⁇ 7, such as heptane.
  • It provides a method of preparing a compound represented by the formula (I) comprising the step of reacting a compound represented by the formula (II) and a hydrogen donor under a catalyst represented by the formula (III) or (IV) .
  • * represents a Chiral center
  • the present invention provides a compound of formula I-1 comprising chiral reduction of a compound represented by formula II under a catalyst represented by formula III to prepare a compound represented by formula I-1. It provides a method for producing the compound represented.
  • the present invention provides a compound of formula I-2 comprising chiral reduction of a compound represented by formula II under a catalyst represented by formula IV to produce a compound represented by formula I-2 It provides a method for producing the compound represented.
  • a compound of Formula I may be prepared by reacting a compound of Formula II with a hydrogen donor in an organic solvent under a ruthenium catalyst represented by Formula III or Formula IV.
  • a compound of formula (I-1) may be prepared by reacting a compound of formula (II) with a hydrogen donor under a ruthenium catalyst represented by formula (III) as in Scheme I-1.
  • the compound of formula (II) may be prepared by reacting the compound of formula (II) with a hydrogen donor under the catalyst represented by formula (IV), as in Scheme I-2.
  • the method for preparing an optically active chromamanol derivative according to the present invention does not require a separate purification process because it shows high optical purity and does not include harsh reaction conditions. And because it does not use dangerous reagents, it is advantageous for mass production and has a good production yield.
  • the final product prepared by the preparation method can be used to prepare other compounds having a chromamanol structure having an optical activity, in particular as an intermediate for the preparation of compounds that can be used as antibacterial, anti-ulcer, anti-inflammatory drugs Can be used.

Abstract

La présente invention concerne un nouveau procédé de préparation d'un dérivé de chromanol. Selon la présente invention, contrairement à une technique de réduction optiquement active classiquement connue, un procédé de préparation d'un dérivé de chromanol présentant une activité optique présente les avantages : de ne pas nécessiter de procédé de purification supplémentaire, étant donné que le chromanol à préparer présente une pureté optique élevée ; d'être favorable pour une production en masse, étant donné qu'il ne contient pas de conditions de réaction rigoureuses et qu'on n'utilise pas de réactifs dangereux ; et de présenter un excellent rendement de préparation.
PCT/KR2016/008580 2015-08-04 2016-08-03 Nouveau procédé de préparation d'un dérivé de chromanol WO2017023124A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2018505683A JP6676146B2 (ja) 2015-08-04 2016-08-03 クロマノール誘導体の新規な製造方法
CN201680044642.9A CN107849003A (zh) 2015-08-04 2016-08-03 制备色原烷醇衍生物的新方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020150110248A KR101769204B1 (ko) 2015-08-04 2015-08-04 크로마놀 유도체의 신규한 제조방법
KR10-2015-0110248 2015-08-04

Publications (1)

Publication Number Publication Date
WO2017023124A1 true WO2017023124A1 (fr) 2017-02-09

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2016/008580 WO2017023124A1 (fr) 2015-08-04 2016-08-03 Nouveau procédé de préparation d'un dérivé de chromanol

Country Status (4)

Country Link
JP (1) JP6676146B2 (fr)
KR (1) KR101769204B1 (fr)
CN (1) CN107849003A (fr)
WO (1) WO2017023124A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022016309A1 (fr) 2020-07-20 2022-01-27 Hangzhou Duyi Technology Co. Ltd. Procédés de préparation de dérivés de chromanone substitués
CN113237970A (zh) * 2021-04-23 2021-08-10 上海应用技术大学 一种5,7-二氟苯并二氢吡喃-4-醇的r、s异构体的高效液相色谱分离方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008059373A1 (fr) * 2006-11-17 2008-05-22 Raqualia Pharma Inc. Dérivés d'imidazo [1,2-a] pyrazine et leur utilisation comme antagonistes de la pompe à protons
KR20080080195A (ko) * 2005-12-19 2008-09-02 화이자 인코포레이티드 크로메인 치환된 벤즈이미다졸 및 이들의 산 펌프억제제로서의 용도
KR20080108129A (ko) * 2006-03-17 2008-12-11 라퀄리아 파마 인코포레이티드 크로메인 유도체
WO2008151927A2 (fr) * 2007-06-15 2008-12-18 Nycomed Gmbh Dérivés de benzimidazole à substitution 6-n pharmaceutiquement actifs
KR101179302B1 (ko) * 2004-06-22 2012-09-03 노파르티스 아게 퀴놀린 유도체의 거울이성질체 선택적 제조법

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1741693B1 (fr) * 2004-03-29 2011-08-03 Nagoya Industrial Science Research Institute Procede de fabrication d' alcools optiquement actifs
KR101130465B1 (ko) 2005-12-30 2012-03-27 엘지전자 주식회사 스크롤 압축기의 과열방지장치
AR082472A1 (es) * 2010-08-04 2012-12-12 Janssen Pharmaceutica Nv Compuestos con actividad antibacteriana contra clostridium

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101179302B1 (ko) * 2004-06-22 2012-09-03 노파르티스 아게 퀴놀린 유도체의 거울이성질체 선택적 제조법
KR20080080195A (ko) * 2005-12-19 2008-09-02 화이자 인코포레이티드 크로메인 치환된 벤즈이미다졸 및 이들의 산 펌프억제제로서의 용도
KR20080108129A (ko) * 2006-03-17 2008-12-11 라퀄리아 파마 인코포레이티드 크로메인 유도체
WO2008059373A1 (fr) * 2006-11-17 2008-05-22 Raqualia Pharma Inc. Dérivés d'imidazo [1,2-a] pyrazine et leur utilisation comme antagonistes de la pompe à protons
WO2008151927A2 (fr) * 2007-06-15 2008-12-18 Nycomed Gmbh Dérivés de benzimidazole à substitution 6-n pharmaceutiquement actifs

Also Published As

Publication number Publication date
JP6676146B2 (ja) 2020-04-08
KR101769204B1 (ko) 2017-08-17
KR20170016756A (ko) 2017-02-14
CN107849003A (zh) 2018-03-27
JP2018525376A (ja) 2018-09-06

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