WO1994021637A1 - Procede de preparation de derives de carbapenem condense - Google Patents

Procede de preparation de derives de carbapenem condense Download PDF

Info

Publication number
WO1994021637A1
WO1994021637A1 PCT/EP1994/000838 EP9400838W WO9421637A1 WO 1994021637 A1 WO1994021637 A1 WO 1994021637A1 EP 9400838 W EP9400838 W EP 9400838W WO 9421637 A1 WO9421637 A1 WO 9421637A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
formula
protecting group
carboxyl protecting
salt
Prior art date
Application number
PCT/EP1994/000838
Other languages
English (en)
Inventor
Gian Luca Araldi
Original Assignee
Glaxo Spa
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 Glaxo Spa filed Critical Glaxo Spa
Priority to EP94911906A priority Critical patent/EP0689542A1/fr
Priority to PL94310620A priority patent/PL310620A1/xx
Priority to AU64272/94A priority patent/AU6427294A/en
Priority to JP6520645A priority patent/JPH08507776A/ja
Publication of WO1994021637A1 publication Critical patent/WO1994021637A1/fr
Priority to FI954399A priority patent/FI954399A0/fi
Priority to NO953697A priority patent/NO953697L/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to an improved process for the synthesis of an antibacterial agent.
  • European Patent Application publication No. 0416953A2 describes a novel class of tricyclic antibacterial agents and processes for their preparation.
  • a particular preferred compound described therein is the methoxy derivative (I)
  • (I) may be prepared by the process as outlined below:-
  • a is a hydroxyl protecting group
  • R2a is a carboxyl protecting group
  • Y is oxygen or a phosphine group.
  • R is a carboxyl protecting group followed by removal of the carboxyl protecting to give either the free carboxylic acid or a physiologically acceptable salt thereof.
  • Suitable carboxyl protecting groups R include allyl or arylmethyl such as benzyl, t-butylbenzyl, diphenylmethyl or p-biphenylmethyl.
  • the thermal cyclisation process is preferably carried out by heating the compound of formula (II) in a solvent at a temperature within the range 40- 200°-.
  • suitable solvents include hydrocarbons such as toluene or xylene, ethers such as tetrahydrofuran or 1 ,4-dioxan or an alkanol e.g. propanol or isopropanol, or esters such as ethyl acetate or mixtures of two or more such solvents.
  • the carboxyl protecting group R may be removed by standard processes such as those described in Protective Groups in Organic Chemistry, pages 192-210, Edited by J F W McOmie (Plenum Press 1983).
  • R represents an arylmethyl group this may be removed by conventional procedures using hydrogen and a metal catalyst e.g. palladium in a suitable solvent such as an alkanol e.g. propanol and preferably in the presence of a tertiary amine such as a trialkylamine e.g. triethylamine.
  • group R represents an allyl group then this is preferably removed by treatment with an allyl acceptor in the presence of tetrakis(triphenylphospine) palladium and optionally in the presence of triphenylphospine.
  • Suitable allyl acceptors include sterically hindered amines such as t-butylamine, cyclic secondary amines such as morpholine or thiomorpholine, tertiary amines such as triethylamine, aliphatic or cycloaliphatic ⁇ -dicarbonyl compounds such as acetylacetone, ethyl acetoacetate or dimedone, or alkanoic acids or alkali metal salts thereof such as acetic acid, propionic acid or 2-ethyl hexanoic acid or the potassium or sodium salt thereof.
  • the reaction is preferably carried out in an inert solvent such as an ether e.g.
  • diethyl ether or tetrahydrofuran an alkanol e.g. ethanol, or propanol, an ester e.g. ethyl acetate or a halohydrocarbon e.g. methylene chloride, or mixtures thereof.
  • the reaction is conveniently carried out in the temperature range 0-40° more particularly at room temperature.
  • the thermal cyclisation is carried out using a compound of formula (III) wherein R is an arylmethyl group such as benzyl or p-t-butylbenzyl and at a temperature within the range 40-120° and in a solvent such as a hydrocarbon e.g. toluene, an ether e.g. 1 ,4-dioxan or an alkanol e.g. propanol or isopropanol or an ester e.g. ethylacetate or a mixture thereof with an alkanol.
  • a solvent such as a hydrocarbon e.g. toluene, an ether e.g. 1 ,4-dioxan or an alkanol e.g. propanol or isopropanol or an ester e.g. ethylacetate or a mixture thereof with an alkanol.
  • the arylmethyl carboxyl protecting group R is preferably removed by hydrogenolysis using hydrogen and a metal catalyst such as palladium and in a solvent such as an alkanol e.g. ethanol, isopropanol, esters e.g. ethyl acetate or ketone e.g. acetone and in the presence of a base.
  • Suitable bases for use in the reaction include tertiary organic bases such as trialkylamines e.g. triethylamine.
  • the carboxylic acid (I) or a salt thereof may conveniently be converted into a physiologically acceptable salt thereof without isolation of the product of the hydrogenolysis.
  • the sodium salt thereof may be obtained by the addition of acetone and sodium ethylhexanoate to the reaction solution, followed by addition of a non solvent such as an ether e.g. diisopropyl ether. In this process it may be advantageous to add seed crystals of the required sodium salt.
  • a non solvent such as an ether e.g. diisopropyl ether.
  • Salts of the compound of formula (I) include physiologically acceptable salts thereof and non physiologically acceptable salts thereof.
  • Suitable physiologically acceptable salts of compound of formula (I) include salts formed with alkali metals e.g. sodium or potassium, alkaline earth metals e.g. calcium, amino acids (e.g. lysine and arginine) and organic bases (e.g. procaine, phenylbenzylamine, ethanolamine, diethanolamine and N-methyl glucosamine).
  • alkali metals e.g. sodium or potassium
  • alkaline earth metals e.g. calcium amino acids (e.g. lysine and arginine) and organic bases (e.g. procaine, phenylbenzylamine, ethanolamine, diethanolamine and N-methyl glucosamine).
  • amino acids e.g. lysine and arginine
  • organic bases e.g. procaine, phenylbenzylamine, ethanolamine, diethanolamine and N-methyl glucosamine.
  • hydroxy compounds of formula (II) which are novel and represent another aspect of the invention may be prepared from the corrresponding ether (III)
  • H- ⁇ is a trialkylsilyl group and R is as defined in formula (II) by conventional procedures.
  • is a t-butyldimethysilyl group this may be removed by treatment with tetrabutyiammonium fluoride and acetic acid in a solvent such as tetrahydrofuran or by hydrolysis with a mineral acid such as hydrochloric acid in a suitable organic solvent, for example acetonitrile and acetic acid.
  • silylethers of formula (III) are either known compounds or may be prepared by the procedures described in EPA No. 0416953A2 and or the examples given below.
  • the aqueous layer was re-extracted with ethyl acetate (15 ml) and the combined organic phases were washed with 1 M a solution of citric acid (40 ml), water (20 ml) and brine (20 ml).
  • the organic solution was treated with 2,6-lutidine (2.5 ml), sodium bromide (2.25 g) and triphenylphosphine (5.7 g).
  • the resultant mixture was stirred at 25 C for 20 hours after that was washed with 1 M solution of citric acid (25 ml), water (25 ml) and brine (3x50 ml).

Abstract

Procédé de préparation d'un composé antibactérien répondant à la formule (I), ou de son sel, comportant la cyclisation thermique d'un composé répondant à la formule (II), dans laquelle R représente un groupe de protection carboxylique, suivie de l'élimination dudit groupe de protection carboxylique R, et éventuellement de la transformation en son sel de l'acide carboxylique ainsi obtenu.
PCT/EP1994/000838 1993-03-20 1994-03-17 Procede de preparation de derives de carbapenem condense WO1994021637A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP94911906A EP0689542A1 (fr) 1993-03-20 1994-03-17 Procede de preparation de derives de carbapenem condense
PL94310620A PL310620A1 (en) 1993-03-20 1994-03-17 Method of obtaining condenset carbapenemic derivatives
AU64272/94A AU6427294A (en) 1993-03-20 1994-03-17 Process for the preparation of condensed carbapeneme derivatives
JP6520645A JPH08507776A (ja) 1993-03-20 1994-03-17 化学的方法
FI954399A FI954399A0 (fi) 1993-03-20 1995-09-18 Kemiallinen prosessi
NO953697A NO953697L (no) 1993-03-20 1995-09-19 Kjemisk fremgangsmåte

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB939305813A GB9305813D0 (en) 1993-03-20 1993-03-20 Chemical process
GB9305813.9 1993-03-20

Publications (1)

Publication Number Publication Date
WO1994021637A1 true WO1994021637A1 (fr) 1994-09-29

Family

ID=10732441

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1994/000838 WO1994021637A1 (fr) 1993-03-20 1994-03-17 Procede de preparation de derives de carbapenem condense

Country Status (11)

Country Link
EP (1) EP0689542A1 (fr)
JP (1) JPH08507776A (fr)
CN (1) CN1119864A (fr)
AU (1) AU6427294A (fr)
CA (1) CA2157787A1 (fr)
FI (1) FI954399A0 (fr)
GB (1) GB9305813D0 (fr)
HU (1) HUT73486A (fr)
NO (1) NO953697L (fr)
PL (1) PL310620A1 (fr)
WO (1) WO1994021637A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997006174A1 (fr) * 1995-08-05 1997-02-20 Glaxo Wellcome Spa Procede d'isomerisation
EP2085084A1 (fr) 2008-01-29 2009-08-05 LEK Pharmaceuticals D.D. Utilisation d'inhibiteur de lactamases bêta et sa combinaison avec les antibiotiques de lactamases bêta
WO2018206466A1 (fr) 2017-05-08 2018-11-15 Glaxosmithkline Intellectual Property Development Limited Sanfétrinem ou un sel ou ester de celui-ci destiné à être utilisé dans le traitement d'une infection mycobactérienne

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0102239A1 (fr) * 1982-08-24 1984-03-07 Sankyo Company Limited Dérivés d'azétidinone, un procédé pour leur préparation et leur application comme intermédiaires dans la préparation d'antibiotiques du type carbapénème
EP0416953A2 (fr) * 1989-09-08 1991-03-13 GLAXO S.p.A. Dérivés d'acide 10-(1-hydroxyéthyl)-11-oxo-1-azatricyclo[7.2.0.0.3,8]undéc-2-ène-2-carboxylique
EP0507313A1 (fr) * 1991-04-05 1992-10-07 Takeda Chemical Industries, Ltd. Composés polycycliques de carbapénèmes, leur préparation et leur utilisation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0102239A1 (fr) * 1982-08-24 1984-03-07 Sankyo Company Limited Dérivés d'azétidinone, un procédé pour leur préparation et leur application comme intermédiaires dans la préparation d'antibiotiques du type carbapénème
EP0416953A2 (fr) * 1989-09-08 1991-03-13 GLAXO S.p.A. Dérivés d'acide 10-(1-hydroxyéthyl)-11-oxo-1-azatricyclo[7.2.0.0.3,8]undéc-2-ène-2-carboxylique
EP0507313A1 (fr) * 1991-04-05 1992-10-07 Takeda Chemical Industries, Ltd. Composés polycycliques de carbapénèmes, leur préparation et leur utilisation

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997006174A1 (fr) * 1995-08-05 1997-02-20 Glaxo Wellcome Spa Procede d'isomerisation
US6025487A (en) * 1995-08-05 2000-02-15 Glaxo Wellcome Spa Isomerisation process
EP2085084A1 (fr) 2008-01-29 2009-08-05 LEK Pharmaceuticals D.D. Utilisation d'inhibiteur de lactamases bêta et sa combinaison avec les antibiotiques de lactamases bêta
WO2018206466A1 (fr) 2017-05-08 2018-11-15 Glaxosmithkline Intellectual Property Development Limited Sanfétrinem ou un sel ou ester de celui-ci destiné à être utilisé dans le traitement d'une infection mycobactérienne
RU2757272C2 (ru) * 2017-05-08 2021-10-12 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед Санфетринем или его соль или сложный эфир для применения при лечении микобактериальной инфекции
US11253500B2 (en) 2017-05-08 2022-02-22 Glaxosmithkline Intellectual Property Development Limited Sanfetrinem or a salt or ester thereof for use in treating mycobacterial infection

Also Published As

Publication number Publication date
NO953697D0 (no) 1995-09-19
EP0689542A1 (fr) 1996-01-03
FI954399A (fi) 1995-09-18
FI954399A0 (fi) 1995-09-18
HU9502738D0 (en) 1995-11-28
HUT73486A (en) 1996-08-28
AU6427294A (en) 1994-10-11
GB9305813D0 (en) 1993-05-05
NO953697L (no) 1995-09-19
CA2157787A1 (fr) 1994-09-29
CN1119864A (zh) 1996-04-03
JPH08507776A (ja) 1996-08-20
PL310620A1 (en) 1995-12-27

Similar Documents

Publication Publication Date Title
Narasaka et al. Total synthesis of a macrocyclic pyrrolizidine alkaloid,(.+-.)-integerrimine, utilizing an activable protecting group
JPH04134077A (ja) イソオキサゾール化合物
JPH0557980B2 (fr)
WO1994021637A1 (fr) Procede de preparation de derives de carbapenem condense
WO2012062035A1 (fr) Procédé de synthèse pour le méropénem
EP0006355B1 (fr) Anhydride mixte qui est un intermédiaire de synthèse de stéroides et procédé de préparation de produits intermédiaires de synthèse de stéroides
EP0273321B1 (fr) Dérivés de la bromo-7 bêta-carboline et procédé pour leur préparation
EP0689543B1 (fr) Procede de preparation de derives de carbapenem condense
EP0379063B1 (fr) Procédé de préparation des dérivés de DL-Proline (trans)-4-subsituée
CN1043992C (zh) 制备中氮茚衍生物的新方法
US6143885A (en) Preparation of beta-methyl carbapenem intermediates
Mihovilovic et al. An Efficient and Simple Procedure for the Preparation of α‐Keto‐β‐lactams
US5849907A (en) Chemical process
JP3748933B2 (ja) １−置換アゼチジノン誘導体の製造法
EP1007511B1 (fr) Preparation d'intermediaires de beta-methyl carbapenem
US4234491A (en) Steroid synthesis process using mixed anhydride
JP3159518B2 (ja) アミノ置換スピロ化合物の製法
JP2652047B2 (ja) ４−ベンゾイルオキシ−３−ヒドロキシエチルアゼチジン−２−オン誘導体の製造方法
JPH0713058B2 (ja) ４―置換アゼチジノン誘導体の製造方法
JPH0220637B2 (fr)
JPS6334147B2 (fr)

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 94191532.8

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR BY CA CH CN CZ DE DK ES FI GB GE HU JP KG KP KR KZ LK LU LV MD MG MN MW NL NO NZ PL PT RO RU SD SE SI SK TJ TT UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2157787

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1994911906

Country of ref document: EP

Ref document number: 954399

Country of ref document: FI

ENP Entry into the national phase

Ref document number: 1995 513873

Country of ref document: US

Date of ref document: 19951006

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: 1994911906

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1994911906

Country of ref document: EP