KR0144453B1 - 베타-락타마제 저해제의 제조 방법 - Google Patents

베타-락타마제 저해제의 제조 방법

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Publication number
KR0144453B1
KR0144453B1 KR1019900006740A KR900006740A KR0144453B1 KR 0144453 B1 KR0144453 B1 KR 0144453B1 KR 1019900006740 A KR1019900006740 A KR 1019900006740A KR 900006740 A KR900006740 A KR 900006740A KR 0144453 B1 KR0144453 B1 KR 0144453B1
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South Korea
Prior art keywords
solution
methoxyphenol
methyl
filtrate
lactamase
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KR1019900006740A
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KR900018115A (ko
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크리쉬난 라가반
갬블 제시
블룸 데이빗
브이 커런 윌리엄
제이 리이 빙
비이 콘로우 랜섬
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알퐁스 아아르 노에
아메리칸 사이아나밋드 캄파니
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Publication of KR900018115A publication Critical patent/KR900018115A/ko
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • C07D499/86—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with only atoms other than nitrogen atoms directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

내용 없음

Description

베타-락타마제 저해제의 제조 방법
본 발명은 하기 구조식을 갖는, 중간물질［2S-(2α,3β,5α)］-3-메틸-7-옥소-3-(1H-1,2,3-트리아졸-1-일메틸)-4-티아-1-아자비시클로［3.2.0］헵탄-2-카르복실산, (4-니트로페닐)-메틸 에스테르, 4,4-디옥사이드를 제조하는 개선된 방법에 관한 것이다.
Figure kpo00001
개선점은 증가된 수율(60%) 및 순도(90%)에 있으며, 지금까지 공지된 합성에 있어서의 두 단계를 제거시켜 크로마토그래피시키지 않고 반응 혼합물로부터 직접 분리를 허용한다.
그런다음 상기 중간 물질은 하기 구조식을 갖는 생물학적으로 활성적인 β-락타마제 저해제［2S-(2α,3β,5α)］-3-메틸-7-옥소-3-(1H-1,2,3-트리아졸-1-일메틸)-4-티아-1-아자비시클로［3.2.0］헵탄-2-카르복실산, 4,4-디옥시이드를 생성시키기 위해 사용된다.
Figure kpo00002
본 발명의 주제인 방법의 개선점은 하기 반응 도표 및 기술에 의해기술된다:
Figure kpo00003
상기 반응에 따라 아지도페닐설폰 1은 비닐 프로피오네이트를 함유하는 4-메톡시페놀안에 용해되고 이 용액은 70-80℃에서 톨루엔내 4-메톡시페놀 및 비스(트리메틸실릴)아세트아미드 용액과 적가 반응된 다음 약 24시간 동안 95-100℃에서 반응되고 여과되고 냉각되어 90% 순도 및 60% 수율의 중간물질［2S-(2α,3β,5α)］-3-메틸-7-옥소-3-(1H-1,2,3-트리아졸-1-일메틸)-4-티아-1-아자비시클로［3.2.0］헵탄-2-카르복실산, (4-니트로페닐)메틸에스테르, 4,4-디옥사이드, 2을 생성시킨다.
그런다음 중간물질 2는 중탄산 나트륨을 함유하는 에틸 아세테이트/물안의 탄소상 5% 팔라듐위에서 수소처리된 다음 광산으로 산성화되어, 원하는 β-락타마제 저해제 3를 얻는다.
[실시예 1]
［2S-(2α,3β,5α)］-3-메틸-7-옥소-3-(1H-1,2,3-트리아졸-1-일메틸)-4-티아-1-아자비시클로［3.2.0］헵탄-2-카르복실산, (4-니트로페닐)-메틸 에스테르 4,4-디옥사이드
84g의 아지도페남설폰을 함유하는 에틸아세테이트 용액을 건조 상태로 증발시킨 다음, 1865ml의 비닐 프로피오네이트를 함유하는 4g의 4-메톡시페놀에 첨가시키고 1시간 동안 휘저어 섞었다. 용액을 여과시키고 여액을 3.5시간에 걸쳐 70-80℃에서 1324ml의 톨루엔, 84ml(66.8g)의 비스(트리메틸실릴)아세트아미드 및 4g의 4-메톡시페닐로 구성된 용액에 적가시켰다. 첨가가 다 이루어진 경우 반응 온도를 95-100℃로 올리고 24시간 동안 유지시켰다. 그런다음 반응물을 실온으로 냉각시키고, 11g의 함수의 규산 마그네슘과 조합시키고, 20분 동안 휘저어 섞은 다음, 33g의 함수의 규산 마그네슘의 베드를 통해 여과시켰다. 여액을 회전증발시켜 2500ml의 증류수를 수집했다. 여액을 12시간 동안 실온에서 휘저어 섞은 다음, 2시간 동안 0-5℃로 냉각시키고 결과 형성된 고형물을 수집하고, 헵탄으로 세척하고 건조시켜 90% 순도를 갖는 50g의 원하는 중간물질을 얻었다.

Claims (1)

  1. 아지도페남설폰, 4-메톡시페놀 및 비닐프로피오네이트 용액을 톨루엔내 비스(트리메틸실릴)아세트아미드 및 4-메톡시페놀 용액과 80-100℃에서 18-30시간 동안 반응시킨 다음 결과 형성된 용액을 여과시키고 여액을 0-10℃로 냉각시키는 것으로 구성되는 화합물［2S-(2α,3β,5α)］-3-메틸-7-옥소-3-(1H-1,2,3-트리아졸-1-일메틸)-4-티아-1-아자비시클로［3.2.0］헵탄-2-카르복실산, (4-니트로페닐)메틸 에스테르, 4,4-디옥사이드의 제조 방법.
KR1019900006740A 1989-05-12 1990-05-11 베타-락타마제 저해제의 제조 방법 KR0144453B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US07/350,966 1989-05-12
US7/350,966 1989-05-12
US07/350,966 US4958020A (en) 1989-05-12 1989-05-12 Process for producing β-lactamase inhibitor

Publications (2)

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KR900018115A KR900018115A (ko) 1990-12-20
KR0144453B1 true KR0144453B1 (ko) 1998-07-15

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US (1) US4958020A (ko)
EP (1) EP0396901B1 (ko)
JP (1) JP2909145B2 (ko)
KR (1) KR0144453B1 (ko)
AT (1) ATE124048T1 (ko)
CA (1) CA2016500C (ko)
DE (1) DE69020240T2 (ko)
DK (1) DK0396901T3 (ko)
ES (1) ES2073471T3 (ko)
HU (1) HU206724B (ko)

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Publication number Priority date Publication date Assignee Title
JP3306473B1 (ja) * 2001-05-01 2002-07-24 大塚化学株式会社 β−ラクタム化合物の無水結晶及びその製造法
US20060173177A1 (en) * 2005-01-28 2006-08-03 Gego Csaba L Process for preparation of penam derivatives
US20070286818A1 (en) * 2006-06-07 2007-12-13 Wyeth Treating cystic fibrosis with antibiotics via an aerosol drug
US20070286817A1 (en) * 2006-06-07 2007-12-13 Wyeth Treating cystic fibrosis with antibiotics via a swirler delivery

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS58225091A (ja) * 1982-06-21 1983-12-27 Taiho Yakuhin Kogyo Kk ペニシリン誘導体及びその製造法
AU541028B2 (en) * 1982-06-21 1984-12-13 Taiho Pharmaceutical Co., Ltd. 6-unsubstituted penicillin derivatives
US4562073A (en) * 1982-12-24 1985-12-31 Taiho Pharmaceutical Company Limited Penicillin derivatives
US4496484A (en) * 1983-04-22 1985-01-29 Taiho Pharmaceutical Company, Limited Penicillin derivatives
CA1239392A (en) * 1983-10-13 1988-07-19 Shigeru Yamabe Penicillin derivatives and process for preparing the same
JPS61126087A (ja) * 1984-11-26 1986-06-13 Taiho Yakuhin Kogyo Kk ２α−メチル−２β−（１，２，３−トリアゾ−ル−１−イル）メチルペナム−３α−カルボン酸誘導体の製造法
JPS63112588A (ja) * 1986-10-27 1988-05-17 Denki Kagaku Kogyo Kk トリアゾ−ル誘導体の製造方法

Also Published As

Publication number Publication date
JPH02311482A (ja) 1990-12-27
US4958020A (en) 1990-09-18
HU903007D0 (en) 1990-09-28
ES2073471T3 (es) 1995-08-16
JP2909145B2 (ja) 1999-06-23
ATE124048T1 (de) 1995-07-15
EP0396901B1 (en) 1995-06-21
DE69020240D1 (de) 1995-07-27
DE69020240T2 (de) 1996-04-04
HUT54693A (en) 1991-03-28
CA2016500A1 (en) 1990-11-12
DK0396901T3 (da) 1995-08-14
KR900018115A (ko) 1990-12-20
HU206724B (en) 1992-12-28
CA2016500C (en) 2000-11-28
EP0396901A1 (en) 1990-11-14

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