+

WO1996012712A1 - Derives phosphates reactifs d'acide thiazolylacetique, et procede de preparation d'antibiotiques a base de cephalosporines utilisant ces derives - Google Patents

Derives phosphates reactifs d'acide thiazolylacetique, et procede de preparation d'antibiotiques a base de cephalosporines utilisant ces derives Download PDF

Info

Publication number
WO1996012712A1
WO1996012712A1 PCT/KR1995/000136 KR9500136W WO9612712A1 WO 1996012712 A1 WO1996012712 A1 WO 1996012712A1 KR 9500136 W KR9500136 W KR 9500136W WO 9612712 A1 WO9612712 A1 WO 9612712A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
alkyl
group
represents hydrogen
preparing
Prior art date
Application number
PCT/KR1995/000136
Other languages
English (en)
Inventor
Tae-Won Kang
Woong-Sig Moon
Yoon-Whan Choi
Ki-Jun Hwang
Original Assignee
Miwon Co., Ltd.
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
Priority claimed from KR1019940027118A external-priority patent/KR960014131A/ko
Priority claimed from KR1019940027418A external-priority patent/KR960014143A/ko
Application filed by Miwon Co., Ltd. filed Critical Miwon Co., Ltd.
Publication of WO1996012712A1 publication Critical patent/WO1996012712A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • 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
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
    • C07F9/6539—Five-membered rings
    • 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 a novel reactive phosphate derivative of thiazolylacetic acid which is useful as an intermediate for preparing cephalosporin antibiotics, a process for preparation thereof and a process for preparing cephalosporin antibiotics using the same. More sepcifically, the present invention relates to a novel reactive phosphate derivative of thiazolylalky- loxyiminoacetic acid having the following gormula (II) :
  • R represents hydrogen, C 1 ⁇ C 4 alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C 1 -C 4 alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group; and R 1 represents C 1 ⁇ C 4 alkyl, and to a process for preparing thereof.
  • the present invention also relates to a process for preparing cephalosporin antibiotics using the said reactive phosphate derivative of formula (II) .
  • the cephalosporin antibiotic compounds have been generally prepared by converting the starting organic acid compound represented by the' following formula (I) into the reactive derivative thereof, which is then sub ⁇ jected to acylation reaction with the amino group of beta- lactam nucleus of 7-aminocephalosporanic acid (hereinaf ⁇ ter, referred to as "7-ACA”) to form an amide linkage.
  • 7-ACA beta- lactam nucleus of 7-aminocephalosporanic acid
  • R represents hydrogen, C 1 ⁇ C 4 alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent 1 -C 4 alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group.
  • an acid chloride, a reactive ester, a reac ⁇ tive amide or a mixed acid anhydride has been generally used.
  • the acid chloride is pre- pared by reacting the organic acid compound of formula (I) with a chlorinating agent such as thionyl chloride, phos ⁇ phorus trichloride, phosphorus oxychloride or phosphorus pentachloride at lower temperature and then is reacted with 7-ACA derivative to prepare the desired cephalosporin antibiotic compound (see, U.S. Patent Specification 4,202,893, British Early Published Patent No.
  • the compound of formula (I) can be con- verted into the reactive ester which is then used for preparing the cephalosporin compounds.
  • the organic acid of formula (I) is reacted with 1-hydroxybenzotriazole or 2-mercaptobenzothiazole in the presence of dicyclohexylcarbodiimide (hereinafter, re- ferred to as "DCC") to produce the reactive ester of the organic acid which is then reacted with the 7-ACA deriva ⁇ tive to prepare the desired cephalosporin antibiotic compound.
  • DCC dicyclohexylcarbodiimide
  • R 1 represents hydrogen or an amin ⁇ -protecting group
  • R 2 represents hydrogen, C 1 -C 4 alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb are identical to or different from each other and Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group
  • R 3 represents ⁇ -C ⁇ j alkyl or phenyl or R 3 together with the oxygen and phosphorus atoms to which it is at- tached can form a 5- to 6-membered heterocyclic ring
  • Q represents N or CH.
  • reactive thiophosphate deriva- tive achieves the desired improvement in view of the reactivity and stability, it has- some disadvantages in that before the reactive thiophosphate derivative (A) as synthesized is used in the acylation reaction, the reac ⁇ tion mixture should be subjected to additional steps for neutralization, layer separation, concentration, recrys- tallization, filtration and drying in order to remove the by-products including catalyst, base, etc., and the de- sired final cephalosporin derivative prepared form the reactive thiophosphate compound (A) has undesirable color and odor originated from the sulfur compound produced from the reactive thiophosphate derivative.
  • R represents hydrogen, - ⁇ - ⁇ alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C ⁇ -C ⁇ alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group; and R 1 represents C ⁇ -C ⁇ alkyl.
  • R represents hydrogen, ⁇ -C ⁇ alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C ⁇ -C ⁇ alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group; and R 1 represents ⁇ -C 4 alkyl, characterized in that an aminothiazole derivative repre ⁇ sented by the following formula (I) :
  • R represents hydrogen, C 1 -C 4 alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C 1 -C 4 alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 2 -C 7 cycloalkyl, and Re represents hydroegn or a carboxyl-protecting group;
  • X represents O, S or N and R 3 represents a group of for-
  • R is defined as above and R 1 represents C ⁇ - ⁇ alkyl, is reacted with an 7-ACA derivative represented by the following formula (IV) :
  • X and R 3 are defined as above and R represents hydrogen or a carboxyl-protecting group, in an organic solvent in the presence or absence of a base.
  • Figure 1 is IR spectrum of the reactive phosphate derivative prepared in Example 2 according to the present invention.
  • Figure 2 is 1 H-NMR spectrum of the reactive phosphate derivative prepared in Example 2 according to the present invention.
  • Figure 3 is 1 C-NMR spectrum of the reactive phosphate derivative prepared in Example 2 according to the present invention.
  • the present invention relates to novel reactive phosphate derivative of thiazolylalkyloxyi- minoacetic acid represented by the following formula (II) , which is useful as an intermediate in preparing cephalos ⁇ porin antibiotic compounds:
  • R represents hydrogen, C 1 -C 4 alkyl or a group of formula -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C 1 -C 4 alkyl or Ra and Rb together with the carbon atom to which they are attached can form C 3 -C 7 cycloalkyl, and Re represents hydrogen or a carboxyl-protecting group; and R 1 represents C - ⁇ alkyl.
  • any protecting group which is conventionally used in the field of preparation of cephalosporin antibiotics can be used.
  • lower alkanesulfonyl(lower)alkyl e.g. 2-mesylethyl, etc,
  • lower alkoxycarbonyloxy(lower) alkyl e.g. methoxycarbonyloxymethyl, ethoxycarbonyloxy- methyl, propoxycarbonyloxymethyl, etc.
  • lower alkenyl e.g. vinyl, allyl, etc.
  • lower alkynyl e.g.
  • aryl(lower)alkyl e.g. benzyl, 4-methoxybenzyl , phenylethyl, trityl, benzhydryl, etc.
  • optionally substituted aryl e.g. phenyl, 4-chlorophenyl , tolyl, t-butylphenyl , xylyl, mesityl, cumenyl, etc.
  • tri (lower) alkylsilyl e.g.
  • trime- thylsilyl trime- thylsilyl, triethylsilyl, isopropylidenedimethylsilyl, t- butyldimethylsilyl, diisopropylmethylsilyl, etc.) , tria- rylsilyl (e.g. triphenylsilyl, etc.), triaryl (lower) alkyl ⁇ silyl (e.g. tribenzylsilyl, etc.) , diaryl (lower) alkylsilyl (e.g. diphenyl t-butylsilyl) , and the like groups.
  • tria- rylsilyl e.g. triphenylsilyl, etc.
  • triaryl (lower) alkyl ⁇ silyl e.g. tribenzylsilyl, etc.
  • diaryl (lower) alkylsilyl e.g. diphenyl t-butylsilyl
  • the preferable one of the reactive phosphate derivative of formula (II) accord ⁇ ing to the present invention is the compound wherein R represents C 1 ⁇ C 4 alkyl or a group -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb independently of one another represent C,-C 4 alkyl and Re represents hydrogen or C 1 -C 4 alkyl, and R 1 represents C,-C 2 alkyl.
  • Particularly preferred reactive phosphate derivative of formula (II) is the compound wherein R represents methyl or a group -C(Ra) (Rb)C0 2 Rc wherein Ra and Rb inde ⁇ pendently of one another represent methyl and Re repre ⁇ sents hydrogen or butyl, and R represents ethyl.
  • the pesent invention relates to a process for preparing the compound of formula (II) .
  • the desired reactive phosphate derivative of formula (II) can be obtained by reacting an organic acid of formula (I) with a phosphate compound of formula (III) .
  • the process for preparing the reactive phosphate derivative of formula (II) according to the present invention can be represented by the following reaction scheme.
  • R and R 1 are defined as above.
  • the phos- phate compound of formula (III) is generally used in the ratio of 0.5 to 1.5 equivalent weight, preferably 0.95 to 1.05 equivalent weight, with respect to one equivalent weight of the organic acid of formula (I) .
  • Suitable catalyst which can be used in the present inven- tion includes tertiary amines such as triethylamine, 2,6- lutidine, diethylisopropylamine, pyridine, N,N'- dimethylaminopyridine, r-picoline, etc., quaternary ammo ⁇ nium salts such as tetra ethylguanidine, etc., or saccha- rin, with saccharin being most preferably used.
  • tertiary amines such as triethylamine, 2,6- lutidine, diethylisopropylamine, pyridine, N,N'- dimethylaminopyridine, r-picoline, etc.
  • quaternary ammo ⁇ nium salts such as tetra ethylguanidine, etc.
  • saccha- rin with saccharin being most preferably used.
  • the reaction can be practiced in the absence of a cata ⁇ lyst, in general, the reaction is preferably carried out in the presence of a catalyst since the reaction under the catalyst does not produce any reaction by-product and can be completed within a short period under mild reaction condition. It is preferable to use the catalyst in the molar ratio of 0.1 to 5% with respect to the organic acid of formula (I) .
  • This reaction can be preferably carried out in the presence of a solvent.
  • a solvent which is suitable for this purpose, any organic solvent which does not adversely affect the reaction can be used.
  • a polar or non-polar solvent for example, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, xylene, acetone, acetonitrile, ethyl acetate, dioxane, tetrahy- drofuran, NjN'-dimethylformamide, N,N'-dimethylacetamide, dimethylsulfoxide, etc.
  • a mixture of two or more solvents can also be used.
  • the above reaction according to the present invention can be preferably carried out in the presence of a base to remove the acid (HC1) liberated from the reaction.
  • the base which can be suitably used for this purpose includes diisopropylethylamine, triethylamine, diethylamine, tri-n- butylamine, tetramethylguanidine, pyridine, 2,6-lutidine, 2,4,6-collidine, etc.
  • the reaction is generally carried out at the tempera ⁇ ture in the range of -40°C to 60°C, and preferably at 25°C.
  • the reaction time is generally 0.5 to 2 hours and preferably 30 minutes.
  • the present invention also relates to a process for preparing cephalosporin compounds of formula (V) using the reactive phosphate derivative of formula (II) , as depicted in the following reaction scheme.
  • R and R 1 are defined as above,
  • R 2 represents hydrogen or a carboxyl-protecting group
  • X represents S, 0 or N and R 3 represents a group of
  • R represents hydrogen or sodium or represents an inter ⁇ nal salt.
  • the cephalosporin anti ⁇ biotic compound of formula (V) can be obtained by acylat- ing 7-ACA derivative of formula (IV) with the reactive phosphate derivative of formula (II) .
  • This reaction can be preferably conducted under conditions conventionally used in preparing the cephalosporin antibiotics.
  • the reactive phosphate derivative of formula (II) used as the intermediate compound in this reaction can be separated, purified and then intro- symbolized in the reaction.
  • the reactive phosphate derivative of formula (II) as prepared is not separated from the reaction solution and is successively subjected to the acylation reaction with the 7-ACA deriva ⁇ tive of formula (IV) to prepare the cephalosporin antibi- otics.
  • R* is a carboxyl-protecting group
  • any of said carboxyl-protecting groups can be suitably used as the protecting group, but the carboxyl group of R 2 is preferably protected in the silylated form.
  • the silylating agent which can be appropriately used for protecting the carboxylic group in the silylated form includes dichloro ethylsilane, trichloromethylsilane, hexa ethyldisilazane, N,0-bis-trimethyIsilylacetamide, N,N'-bis-trimethylsilylurea, etc., with N,0-bis-trimethyl- silylacetamide or N,N'-bis-trimethylsilylurea being most preferably used.
  • the 7-ACA derivative of formula (IV) wherein R is a carboxyl-protecting group, particularly a silyl group is used as the reactant
  • this compound can be previously prepared and then used for the reaction with the reactive phosphate derivative of formula (II) .
  • the compound of formula (IV) can be allowed to participate in the reaction in the form of the compound wherein R 2 is protected by reacting the compound of formu ⁇ la (IV) wherein R is hydrogen with the reactive phosphate derivative of formula (II) in the presence of a silylating agent.
  • the silylating agent can be used in the ratio of 0.1 to 5 equivalent weight, preferably 0.9 to 1.1 equivalent weight, with respect to one equivalent weight of the 7-ACA derivative of formula (IV) wherein R 2 is hydrogen.
  • the above reaction for preparing the cephalosporin derivative of formula (V) according to the present invention can be practiced in the presence of a suitable base and solvent.
  • a suitable base which can be preferably used for this purpose, diisopropylethylamine, triethylamine, diethylamine, tri-n-butylamine, tetrameth ⁇ ylguanidine, pyridine, 2,6-lutidine, 2,4,6-collidine, etc. can be mentioned.
  • the base is used generally in the ratio of 0.1 to 5 equivalent weight, preferably 1 to 3 equivalent weight, with respect to one equivalent weight of the 7-ACA derivative of formula (IV) .
  • any organic solvent which does not adversely affect the rac- tion can be used as the solvent for this reaction, one selected from the group consisting- of methylene chloride, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, chloroform, ethyl acetate, 1,2-dimethoxyethane, dioxane, toluene and benzene, or a mixture of two or more selected therefrom can be preferably used.
  • the acylation reaction of the reactive phosphate derivative of formula (II) with the 7-ACA derivative of formula (IV) generally requires 0.5 to 5 hours and most preferably 1 to 3 hours.
  • the resulting desired cephalosporin antibiotic compound of formula (IV) can be readily separated from the reaction solution by optionally treating with an acid to remove the protecting group with acid hydrolysis and, at the same time, crystallizing and then filtering the product.
  • the acid which can be pref ⁇ erably used for such working-up procedure includes all of the organic acids, hydrochloric acid, phosphoric acid, sulfuric acid, etc. , with dilute hydrochloric acid being preferably used.
  • the resulting compound of formula (V) wherein R 4 is hydrogen can be converted into its sodium salt according to the method conventionally used in the field of preparation of cephalosporin antibi ⁇ otic compounds.
  • (II) can be prepared starting from the compound of formula (I) under mild reaction conditions and then, without separation, reacted with the compound of formula (IV) to prepare the compound of formula (V) , the reaction can be simply conducted in the one-step procedure and, therefore, the desired cephalosporin derivative can be prepared under economically advanta- geous conditions.
  • cephalosporin compound of formula (V) can be prepared without any reaction by-product, it does not require any special procedure and apparatuse for removing by-products.
  • novel reactive phosphate derivative of formula (II) as an acylating agent provides the advan ⁇ tages in that since the final product can be prevented from coloring in comparison with the prior art and, therefore, no recrystallization and purification procedure for removing any color of the product is included, the recovery yield of the final product increases.
  • an analogue of the compound of formula (II) can be prepared using the corre ⁇ sponding analogue of the compound of formula (I)
  • an analogue of the cephalosporin compound of formula (V) can also be synthesized by combining the cephem derivative of formula (IV) with said analogue of the compound of formula (II) in the same manner as mentioned above. All of such cases are included in the present invention.
  • N,N'-dimethylaminopyridine is used instead of saccharin, to obtain 5.3g (Yield 87%) of the same compound as the title compound of Example 1.
  • EXAMPLE 12 The solution of 9.3g(2.9 mmole) of 7-amino-3-methyl- 2,3-cyclopenteno-4-pyridinocephalosporanic acid hydrobro- mide and 5.9g(2.9 mmole) of N,N*-trimethylsilylacetamide dissolved in 100ml of dichloromethane was added dropwise to the dichloromethane solution of the reactive phosphate compound, as prepared in Example 1, over 10 minutes. This mixture was reacted for one hour at 20°C and then 100ml of distilled water was added thereto. The reaction mixture was stirred for 10 minutes to separate the layers.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

Nouveau dérivé phosphaté réactif d'acide thiazolylacétique répondant à la formule générale (II) et étant utilisable comme intermédiaire dans la préparation de dérivés de céphalosporine. Dans la formule générale (II), R représente hydrogène, alkyle C1-4 ou un groupe répondant à la formule -C(Ra)(Rb)CO2Rc, dans laquelle Ra et Rb, indépendamment l'un de l'autre, représentent alkyle C1-4, ou Ra et Rb, pris ensemble avec l'atome de carbone auquel ils sont rattachés, peuvent former cycloalkyle C3-7, et Rc représente hydrogène ou un groupe protecteur de carboxyle; et R1 représente alkyle C¿1-4?. On a également prévu un procédé de préparation de ce dérivé phosphaté réactif de la formule (II), et un procédé de préparation d'antibiotiques à base de céphalosporines utilisant ce dérivé.
PCT/KR1995/000136 1994-10-24 1995-10-23 Derives phosphates reactifs d'acide thiazolylacetique, et procede de preparation d'antibiotiques a base de cephalosporines utilisant ces derives WO1996012712A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR1994/27118 1994-10-24
KR1019940027118A KR960014131A (ko) 1994-10-24 1994-10-24 세펨 유도체의 제조방법
KR1019940027418A KR960014143A (ko) 1994-10-26 1994-10-26 포스페이트 유도체 및 그의 제조방법
KR1994/27418 1994-10-26

Publications (1)

Publication Number Publication Date
WO1996012712A1 true WO1996012712A1 (fr) 1996-05-02

Family

ID=26630632

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR1995/000136 WO1996012712A1 (fr) 1994-10-24 1995-10-23 Derives phosphates reactifs d'acide thiazolylacetique, et procede de preparation d'antibiotiques a base de cephalosporines utilisant ces derives

Country Status (1)

Country Link
WO (1) WO1996012712A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU697970B2 (en) * 1996-06-10 1998-10-22 F. Hoffmann-La Roche Ag Preparation of Cephem- and Isooxacephem derivatives

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3720681A1 (de) * 1986-06-25 1988-01-28 Korea Res Inst Chem Tech 1-methansulfonyloxy- und p-toluolsulfonyloxy-6-trifluormethyl-1h-benzotriazol, 2-heterocyclyl-2-syn-oxyiminoessigsaeure-5-trifluormethyl-1h-benzotriazol-1-yl-ester und deren verwendung zur herstellung von cephalosporinderivaten
JPS63126870A (ja) * 1986-11-17 1988-05-30 Nippon Synthetic Chem Ind Co Ltd:The ２−（２−アミノチアゾ−ル−４−イル）−２−（シン）−ヒドロキシイミノ酢酸エステルの製造法
EP0321966A1 (fr) * 1987-12-23 1989-06-28 Lonza Ag Thioesters et procédé pour leur production

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3720681A1 (de) * 1986-06-25 1988-01-28 Korea Res Inst Chem Tech 1-methansulfonyloxy- und p-toluolsulfonyloxy-6-trifluormethyl-1h-benzotriazol, 2-heterocyclyl-2-syn-oxyiminoessigsaeure-5-trifluormethyl-1h-benzotriazol-1-yl-ester und deren verwendung zur herstellung von cephalosporinderivaten
JPS63126870A (ja) * 1986-11-17 1988-05-30 Nippon Synthetic Chem Ind Co Ltd:The ２−（２−アミノチアゾ−ル−４−イル）−２−（シン）−ヒドロキシイミノ酢酸エステルの製造法
EP0321966A1 (fr) * 1987-12-23 1989-06-28 Lonza Ag Thioesters et procédé pour leur production

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 110, No. 1, 02 January 1989, (Columbus, Ohio, USA), page 754, Abstract No. 8201b, KAWABATA T. et al., "Process for the Preparation of 2-(2-Aminothiazol-4-Yl)-2-(Syn)-(Hydroxyimi no)Acetic Acid Esters"; & JP,A,63 126 870, (30-05-88). *
CHEMICAL ABSTRACTS, Vol. 112, No. 1, 01 January 1990, (Columbus, Ohio, USA), page 735, Abstract no. 7475y, VEVERKA M. et al., "Preparation of (2-Aminothiazol-4-Yl)-(Z)-Oxyiminoacetates in Micellar Dispersions of Reactants"; & CS,A,257 471, (15 February 1989). *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU697970B2 (en) * 1996-06-10 1998-10-22 F. Hoffmann-La Roche Ag Preparation of Cephem- and Isooxacephem derivatives
US5919939A (en) * 1996-06-10 1999-07-06 Hoffmann-La Roche Inc. Preparation of cephem and isooxacephem derivatives
JP2950795B2 (ja) 1996-06-10 1999-09-20 エフ・ホフマン−ラ ロシユ アーゲー セフェム−及びイソオキサセフェム誘導体の製造

Similar Documents

Publication Publication Date Title
US4433141A (en) Intermediate for use in the preparation of cephalosporin antibiotics
JP2766116B2 (ja) セファロスポリン類の新規製造法およびその新規中間体
RU2056425C1 (ru) Производные цефалоспорина или их фармацевтически приемлемые кислотно-аддитивные соли и способы их получения
EP0233271B1 (fr) Procede de preparation d'intermediaires de cephalosporine
CS247080B2 (en) Production method of cefemderivatives
EP0175814B1 (fr) Procédé pour la préparation de dérivés céphem
EP0628561B1 (fr) Procédé pour la préparation de composés de céphalosporines à partir de dérivés réactifs d'acides organiques
JP2505981B2 (ja) 新規なチア（ジア）ゾル酢酸の反応性チオホスフェ―ト誘導体及びその製造方法
JP3434840B2 (ja) 抗生物質セファロスポリンの製造法
HU208828B (en) Process for producing cefalosporins
WO1996012712A1 (fr) Derives phosphates reactifs d'acide thiazolylacetique, et procede de preparation d'antibiotiques a base de cephalosporines utilisant ces derives
US4868294A (en) Process for preparing cephalosporin intermediates
US5317099A (en) Process for the preparation of cephem derivatives
EP0117872B1 (fr) Procede de preparation de composes de cephalosporine
EP0597429B1 (fr) Procédé pour la préparation de 3-vinylcéphalosporines
EP0186463A2 (fr) Bêta-lactames antibiotiques
US4767851A (en) Process for the preparation of 7-amino and 7-substituted amino-desacetoxycephalosporins
KR930007260B1 (ko) 세팔로스포린 유도체의 제조방법
US5162522A (en) Method for producing cephem compounds
CS203983B2 (en) Method of preparing ester of 7-acylamido-3-methyl-3-cephem-4-carboxylic acid
RU2097385C1 (ru) Способ получения производных цефема, реакционноспособные тиофосфатные производные тиа-(или диа)золуксусной кислоты и способ их получения
CH627756A5 (en) Process for the preparation of 3-acyloxymethylcephem compounds
EP0002586B1 (fr) Procédé de scission d'un groupe halogènoacétyl protecteur d'un composé halogènoacétylamino
EP0175544A2 (fr) Procédé pour la préparation d'intermédiaires de céphalosporine
KR0125806B1 (ko) (6R,7R)-7-[(Z)-2(2-아미노티아졸-4-일)-2-(2-t-부톡시카르보닐프로프-2-옥시이미노)아세트아미도]-3-(1-피리디늄메틸)-3-세펨-4-카르복실레이트의 제조방법

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CN HU JP US

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

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载