KR960007601A - How to prepare cefem derivatives - Google Patents

How to prepare cefem derivatives Download PDF

Info

Publication number
KR960007601A
KR960007601A KR1019940020023A KR19940020023A KR960007601A KR 960007601 A KR960007601 A KR 960007601A KR 1019940020023 A KR1019940020023 A KR 1019940020023A KR 19940020023 A KR19940020023 A KR 19940020023A KR 960007601 A KR960007601 A KR 960007601A
Authority
KR
South Korea
Prior art keywords
methoxyimino
iii
reaction
methoxybenzyl
compound
Prior art date
Application number
KR1019940020023A
Other languages
Korean (ko)
Other versions
KR0130941B1 (en
Inventor
강태원
최경석
최윤환
함정엽
이성윤
Original Assignee
유영학
주식회사 미원
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 유영학, 주식회사 미원 filed Critical 유영학
Priority to KR1019940020023A priority Critical patent/KR0130941B1/en
Publication of KR960007601A publication Critical patent/KR960007601A/en
Application granted granted Critical
Publication of KR0130941B1 publication Critical patent/KR0130941B1/en

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
    • C07D501/02—Preparation
    • C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
    • C07D501/06—Acylation of 7-aminocephalosporanic acid
    • 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
    • C07D501/14—Compounds having a nitrogen atom directly attached in position 7
    • C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
    • C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
    • C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

본 발명은 세펨 유도체를 제조하기 위한 신규한 방법을 제공한다. 본 발명의 방법에 따르면 하기 일반식(Ⅱ)의 2-(Z)-메톡시이미노-2-(2-아미노티아졸-4-일)-아세트산을 트리에틸아민 존재하에 트리틸클로라이드와 반응시켜 하기 일반식(Ⅲ)의 2-(Z)-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)-아세트산을 제조 하고; 얻어진 화합물을(Ⅲ)을 수용성 또는 비수용성 용매중에서 트리에틸아민의 존재하에 오염화인을 이용하여 클로리네이션시켜 하기 일반식(Ⅳ)의 2-(Z)-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)-아세틸클로라이드를 제조하며; 얻어진 화합물(Ⅵ)의 수용성 또는 비수용성 용매중에서 탄산수소나트륨 수용액 존재하에 하기 일반식(Ⅴ)의 p-메톡시벤질(6R, 7R)-7-아미노-3-클로로메틸-세펨-4-카르복실레이트(CMC)와 반응시켜 하기 일반식(Ⅰ)의 p-메톡시벤질(6R, 7R)-7-[(Z)-2-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)아세트아미도]-3-클로로메틸세펨-4-카르복실레이트를 제조한다.The present invention provides a novel method for preparing cefem derivatives. According to the method of the present invention, 2- (Z) -methoxyimino-2- (2-aminothiazol-4-yl) -acetic acid of formula (II) is reacted with tritylchloride in the presence of triethylamine 2- (Z) -methoxyimino-2- (2-tritylaminothiazol-4-yl) -acetic acid of the following general formula (III) was prepared; The obtained compound was cloned (III) using phosphorus pentachloride in the presence of triethylamine in an aqueous or non-aqueous solvent to give 2- (Z) -methoxyimino-2- (2- Tritylaminothiazol-4-yl) -acetylchloride; P-methoxybenzyl (6R, 7R) -7-amino-3-chloromethyl-cepem-4-car of the following general formula (V) in the presence of an aqueous sodium hydrogencarbonate solution in an aqueous or non-aqueous solvent of the obtained compound (VI). P-methoxybenzyl (6R, 7R) -7-[(Z) -2-methoxyimino-2- (2-tritylaminothiazole- of the following general formula (I): 4-yl) acetamido] -3-chloromethylcefe-4-carboxylate is prepared.

Description

세펨 유도체를 제조하는 방법How to prepare cefem derivatives

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is an open matter, no full text was included.

Claims (7)

하기 일반식(Ⅱ)의 2-(Z)-메톡시이미노-2-(2-아미노티아졸-4-일)-아세트산을 아세토니트릴중에서 트리에틸아민 존재하에 트리틸클로라이드와 반응시켜 하기 일반식(Ⅲ)의 2-(Z)-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)-아세트산을 제조하고; 얻어진 화합물(Ⅲ)을 수용성 또는 비수용성 용매중에서 트리에틸아민의 존재하에 오염화인을 이용하여 클로리네이션시켜 하기 일반식(Ⅳ)의 2-(Z)-에톡시이미노-2-(2-트리틸아미노티아졸-4-일)-아세틸클로라이드를 제조하며; 얻어진 화합물(Ⅴ)를 수용성 또는 비수용성 용매중에서 탄산수소나트륨 수용액 존재하에 하기 일반식(Ⅴ)의 p-메톡시벤질(6R, 7R)-7-아미노-3-클로로메틸-3-세펨-4-카르복실레이트(CMC)와 반응시켜 하기 일반식(Ⅰ)의 p-메톡시벤질(6R, 7R)-7-[(Z)-2-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)아세트아미도]-3-클로로메틸세펨-4-카르복실레이트를 제조함을 특징으로 하는 p-메톡시벤질(6R, 7R)-7-[(Z)-2-메톡시이미노-2-(2-트리틸아미노티아졸-4-일)아세트아미도]-3-클로로메틸세펨-4-카르복실레이트의 제조방법.2- (Z) -methoxyimino-2- (2-aminothiazol-4-yl) -acetic acid of formula (II) is reacted with tritylchloride in acetonitrile in the presence of triethylamine 2- (Z) -methoxyimino-2- (2-tritylaminothiazol-4-yl) -acetic acid of (III) was prepared; The obtained compound (III) was cloned using phosphorus pentachloride in the presence of triethylamine in an aqueous or non-aqueous solvent to give 2- (Z) -ethoxyimino-2- (2-tri) of the following general formula (IV). Ylaminothiazol-4-yl) -acetylchloride; P-methoxybenzyl (6R, 7R) -7-amino-3-chloromethyl-3-cepem-4 of formula (V) Reacted with -carboxylate (CMC) p-methoxybenzyl (6R, 7R) -7-[(Z) -2-methoxyimino-2- (2-tritylaminothia) P-methoxybenzyl (6R, 7R) -7-[(Z) -2-meth, characterized by preparing zol-4-yl) acetamido] -3-chloromethylcefe-4-carboxylate. A process for preparing methoxyimino-2- (2-tritylaminothiazol-4-yl) acetamido] -3-chloromethylcefe-4-carboxylate. 제1항에 있어서, 각 단계의 반응은 테트라하이드로퓨란, 아세토니트릴, 디클로로메탄, 아세톤, 벤젠, 클로로포름, 에틸아세테이트 및 사염화탄소로 구성된 군에서 선택된 1종 또는 2종 이상의 용매중에서 실시함을 특징으로 하는 방법.The reaction of claim 1, wherein the reaction in each step is carried out in one or two or more solvents selected from the group consisting of tetrahydrofuran, acetonitrile, dichloromethane, acetone, benzene, chloroform, ethyl acetate and carbon tetrachloride. Way. 제1항에 있어서, 화합물(Ⅲ)를 제조하는 반응은 60∼90℃에서 실시함을 특징으로 하는 방법.The process according to claim 1, wherein the reaction for preparing compound (III) is carried out at 60 to 90 ° C. 제1항에 있어서, 화합물(Ⅳ)를 제조하는 반응 -20∼0℃에서 실시함을 특징으로 하는 방법.The process according to claim 1, wherein the reaction is carried out at -20 to 0 캜 to prepare compound (IV). 제1항에 있어서, 화합물(Ⅲ)에 대한 오염화인의 비율은 1.0∼3.0당량임을 특징으로 하는 방법.The method according to claim 1, wherein the ratio of phosphorus pentachloride to compound (III) is 1.0 to 3.0 equivalents. 제1항에 있어서, 탄산수소나트륨의 사용량은 오염화인에 대하여 5.0∼8.0당량임을 특징으로 하는 방법.The method according to claim 1, wherein the amount of sodium bicarbonate used is 5.0 to 8.0 equivalents based on phosphorus pentachloride. 제1항에 있어서, 화합물(Ⅰ)을 제조하는 반응 0∼20℃의 온도에서 실시함을 특징으로 하는 방법.The process according to claim 1, wherein the reaction is carried out at a temperature of 0 to 20 占 폚 for producing compound (I). ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
KR1019940020023A 1994-08-13 1994-08-13 Process for preparing spermidin derivatives KR0130941B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1019940020023A KR0130941B1 (en) 1994-08-13 1994-08-13 Process for preparing spermidin derivatives

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1019940020023A KR0130941B1 (en) 1994-08-13 1994-08-13 Process for preparing spermidin derivatives

Publications (2)

Publication Number Publication Date
KR960007601A true KR960007601A (en) 1996-03-22
KR0130941B1 KR0130941B1 (en) 1998-04-16

Family

ID=19390321

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019940020023A KR0130941B1 (en) 1994-08-13 1994-08-13 Process for preparing spermidin derivatives

Country Status (1)

Country Link
KR (1) KR0130941B1 (en)

Also Published As

Publication number Publication date
KR0130941B1 (en) 1998-04-16

Similar Documents

Publication Publication Date Title
KR860000292A (en) Method for producing benzofuran derivative
KR20030078882A (en) Novel thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin compounds
KR870001332B1 (en) Process for preparing cephem derivatives
KR20040008158A (en) Process for the preparation of cefpodoxime acid
DE3247614A1 (en) CEPHALOSPORINE DERIVATIVES AND METHOD FOR THEIR PRODUCTION
EP0628561B1 (en) Process for preparing cephalosporin compounds from reactive organic acid derivatives
KR960007601A (en) How to prepare cefem derivatives
US6255480B1 (en) Aminothiazole derivatives useful in the preparation of β-lactam antibiotics
EP0117872A1 (en) Process for preparing cephalosporin compounds
SE9401706D0 (en) Process for the preparation of cephem derivatives
KR930016427A (en) Method for preparing ceftriaxone disodium salt hemiheptahydrate
PL145972B1 (en) Method of obtaining cephalosporin
KR0129567B1 (en) The process for preparation of cephalosporins
CA1040620A (en) 6-alkoxy-6-acylamidopenicillins 7-alkoxy-7-acylamido acetoxycephalosporins and process
KR970005893B1 (en) Process for preparing cephalosporin compounds
KR950032213A (en) Manufacturing Method of Cemfe derivatives
KR100361829B1 (en) The process for preparing a ceftriaxone from reactive organic acid derivatives
KR790001045B1 (en) Process for the conversion of 6-aminopenicillanic acid(6-apa) into 7-aminodesacetokyciphalos poranic acid(7-adca)
KR930001114B1 (en) Cephalosporin derivatives
SUGAWARA et al. Synthesis of cephalosporins with substituted thiadiazoles directly attached to the C3-position. I. Synthesis of 3-(5-substituted-1, 3, 4-thiadiazol-2-yl) ceph-3-em derivatives
CA1056816A (en) Process for the conversion of 6-aminopenicillanic acid (6-apa) in 7-aminodesacetoxycephalosporanic acid (7-adca)
KR840004115A (en) Method for preparing cefuroxime derivative
KR100243540B1 (en) Active triazine derivatives of thiazolyl acetic acid and process for preparing them
CA1108121A (en) Process for preparation of 7-alkoxy-3- bromomethylcephems
KR950011448A (en) Process for preparing 7β-[(Z) -2- (2-amino-4-thiazolyl) -2- (carboxymethoxyimino) acetamido] -3-vinyl-3-cefe-4-carboxylic acid

Legal Events

Date Code Title Description
A201 Request for examination
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
LAPS Lapse due to unpaid annual fee