WO2017137784A1 - Procédé de production de mirabegron morphologiquement homogène et de monochlorhydrate de mirabegron - Google Patents

Procédé de production de mirabegron morphologiquement homogène et de monochlorhydrate de mirabegron Download PDF

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Publication number
WO2017137784A1
WO2017137784A1 PCT/HU2016/050045 HU2016050045W WO2017137784A1 WO 2017137784 A1 WO2017137784 A1 WO 2017137784A1 HU 2016050045 W HU2016050045 W HU 2016050045W WO 2017137784 A1 WO2017137784 A1 WO 2017137784A1
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WO
WIPO (PCT)
Prior art keywords
formula
salt
mandelic acid
compound
mirabegron
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/HU2016/050045
Other languages
English (en)
Inventor
András MRAVIK
Tamás Nagy
Attila VIRÁG
Balázs VOLK
Katalin KÁTAINÉ FADGYAS
Mária TÓTHNÉ LAURITZ
Zoltán VARGA
Gábor NÉMETH
András DANCSÓ
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Egis Pharmaceuticals PLC
Original Assignee
Egis Pharmaceuticals PLC
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 Egis Pharmaceuticals PLC filed Critical Egis Pharmaceuticals PLC
Publication of WO2017137784A1 publication Critical patent/WO2017137784A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
    • C07D277/38—Nitrogen atoms
    • C07D277/40—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
    • C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
    • C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
    • 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

Definitions

  • the invention also relates to formula 4a (i?)-mandelic acid salt.
  • the invention also relates to formula 8 (5)-2-[benzyl(4-nitro phenethyl)amino]-l-phenylethanol
  • the desired formula 4 compound is extracted from the mother liquor, which is purified if necessary.
  • the salt of formula 6 or 7 mandelic acid is any chosen alkali metal salt or ammonium salt, preferably sodium, potassium or ammonium salt, preferably sodium salt.
  • the salt of the formula 5 compound is any chosen salt formed with a hydrogen halide, preferably hydrochloride or a salt formed with any univalent organic acid, preferably acetate, or a salt formed with a univalent or multivalent inorganic acid, preferably sulphate, dihydrogen phosphate.
  • the solvent used may be a straight or branched chain alcohol with Ci-C 6 carbon atoms, preferably an aliphatic alcohol with C1-C4 carbon atoms, esters of carboxylic acids with C1-C4 carbon atoms formed with alcohols with C1-C4 carbon atoms, acetonitrile, tetrahydrofuran, dioxane, toluene, t-butyl methyl ether, diisopropyl ether, water or any mixture of two or more of the above solvents.
  • a preferably used solvent may be acetonitrile, isopropyl acetate and ethyl acetate, most preferably ethyl acetate.
  • Sample preparation samples placed between two Mylar sheets, without pulverisation
  • Step duration 109.650 seconds
  • Atmosphere flowing N 2 (50 mL/minute)
  • Sampling frequency 0.1 seconds/point
  • the advantage of the method according to the invention is that by using simple crystallization steps, without the use of toxic solvents, reagents, auxiliary substances, the desired product is obtained in an environmentally friendly, effective and economic way that may be easily implemented at industrial scales.
  • the advantage of the resolving method according to the invention is that under the conditions used a product is obtained with good yield that has exceptionally high chemical and optical purity in one crystallization step, due to which the final product mirabegron, and the mirabegron monohydrochloride salt is also pure.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de production de (R)-2-(2-aminothiazole-4-yl)-4'-[2-[(2-hydroxy-2-phényl)éthylamino]éthyl]acétanilide (mirabegron) de formule 1 et de mirabegron monochlorhydrate de formule 1c, ainsi que les intermédiaires utilisés pendant le procédé.
PCT/HU2016/050045 2016-02-10 2016-09-22 Procédé de production de mirabegron morphologiquement homogène et de monochlorhydrate de mirabegron Ceased WO2017137784A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HUP1600087 2016-02-10
HU1600087A HU231124B1 (hu) 2016-02-10 2016-02-10 Eljárás morfológiailag egységes mirabegron és mirabegron monohidroklorid előállítására

Publications (1)

Publication Number Publication Date
WO2017137784A1 true WO2017137784A1 (fr) 2017-08-17

Family

ID=89992077

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU2016/050045 Ceased WO2017137784A1 (fr) 2016-02-10 2016-09-22 Procédé de production de mirabegron morphologiquement homogène et de monochlorhydrate de mirabegron

Country Status (2)

Country Link
HU (1) HU231124B1 (fr)
WO (1) WO2017137784A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113816864A (zh) * 2020-06-18 2021-12-21 南京正大天晴制药有限公司 一种(r)-2-羟基-n-[2-(4-氨基苯基)乙基]-2-苯乙胺的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1544872A (en) * 1976-06-25 1979-04-25 Sterling Drug Inc 4-hydroxyphenylalkanolamine derivatives and preparation thereof
WO1999020607A1 (fr) * 1997-10-17 1999-04-29 Yamanouchi Pharmaceutical Co., Ltd. Derives amides ou sels desdits derives
CN103387500A (zh) * 2012-05-11 2013-11-13 上海医药工业研究院 一种米拉贝隆及其中间体的制备方法
WO2014132270A2 (fr) * 2013-02-27 2014-09-04 Msn Laboratories Limited Procédé de préparation de monochlorydrate d'acétamide 2- (2-aminothiazol -4-yl)-n- [4- (2- {[ (2r) -2-hydroxy -2-phényl-éthyl] amino} éthyl) phényl], de ses intermédiaires et polymorphe de celui-ci
CN104876890A (zh) * 2014-02-27 2015-09-02 人福医药集团股份公司 化合物的制备工艺

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1544872A (en) * 1976-06-25 1979-04-25 Sterling Drug Inc 4-hydroxyphenylalkanolamine derivatives and preparation thereof
WO1999020607A1 (fr) * 1997-10-17 1999-04-29 Yamanouchi Pharmaceutical Co., Ltd. Derives amides ou sels desdits derives
CN103387500A (zh) * 2012-05-11 2013-11-13 上海医药工业研究院 一种米拉贝隆及其中间体的制备方法
WO2014132270A2 (fr) * 2013-02-27 2014-09-04 Msn Laboratories Limited Procédé de préparation de monochlorydrate d'acétamide 2- (2-aminothiazol -4-yl)-n- [4- (2- {[ (2r) -2-hydroxy -2-phényl-éthyl] amino} éthyl) phényl], de ses intermédiaires et polymorphe de celui-ci
CN104876890A (zh) * 2014-02-27 2015-09-02 人福医药集团股份公司 化合物的制备工艺

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113816864A (zh) * 2020-06-18 2021-12-21 南京正大天晴制药有限公司 一种(r)-2-羟基-n-[2-(4-氨基苯基)乙基]-2-苯乙胺的制备方法
CN113816864B (zh) * 2020-06-18 2024-03-29 南京正大天晴制药有限公司 一种(r)-2-羟基-n-[2-(4-氨基苯基)乙基]-2-苯乙胺的制备方法

Also Published As

Publication number Publication date
HU231124B1 (hu) 2020-12-28
HUP1600087A2 (en) 2017-08-28

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