JP3911008B2 - レバミピドの改良製造法 - Google Patents
レバミピドの改良製造法 Download PDFInfo
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- JP3911008B2 JP3911008B2 JP2006546720A JP2006546720A JP3911008B2 JP 3911008 B2 JP3911008 B2 JP 3911008B2 JP 2006546720 A JP2006546720 A JP 2006546720A JP 2006546720 A JP2006546720 A JP 2006546720A JP 3911008 B2 JP3911008 B2 JP 3911008B2
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- JP
- Japan
- Prior art keywords
- compound
- rebamipide
- formula
- amino acid
- impurity
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/74—Iron group metals
- B01J23/755—Nickel
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明のさらに他の目的は、ブロモメチルカルボスチリル(2)からの目的のレバミピド(1)を製造する過程で、アシル化直前のカルボスチリルアミノ酸化合物(5)に不純物として混在する6−ブロモカルボスチリルアミノ酸化合物(11)を選択的に還元して有用なカルボスチリルアミノ酸化合物(5)に変換させることによって該不純物を除去し、もって、目的とする高純度のレバミピドをより高収率で製造する方法を提供するものである。
HPLC分析で1.09%の2−アミノ−3−[6−ブロモ−2(1H)キノロン−4−イル]プロピオン酸(式(11)の化合物)を不純物として含む、HPLC分析で純度98.56%の2−アミノ−3−[2(1H)キノロン−4−イル]プロピオン酸一塩酸塩二水和物(式(5)の化合物)10gに、水200ml及び25%の水酸化ナトリウム水溶液10mlを加えて溶解した。この水溶液に50%含水展開ラネーニッケル触媒2gを加えて、2気圧の水素雰囲気下、室温で2時間撹拌した後、触媒を濾過した。尚、2時間撹拌後のHPLC分析で、2−アミノ−3−[6−ブロモ−2(1H)キノロン−4−イル]プロピオン酸(式(11)の化合物)は0.01%、2−アミノ−3−[2(1H)キノロン−4−イル]プロピオン酸(式(5)の化合物)は99.73%であった。次に、触媒を濾過した水溶液に25%の水酸化ナトリウム水溶液10mlを加えた後、4−クロロベンゾイルクロリド10gのアセトン50ml溶液を氷冷下で滴下した。滴下終了後、塩酸酸性とし、析出した結晶を濾取した。得られた結晶を水及びアセトンで洗浄し、約80℃で温風乾燥して、11.7g(収率96.2%、HPLC分析の純度99.60%)のレバミピド(1)を得た。
本発明方法によれば、また、その還元反応における溶媒として水を使用し、比較的短時間のうちに温和な条件で実施できるため、目的化合物の大量合成時における操作が簡単である。さらに、前工程の還元反応終了後に、触媒を濾過して除いた塩基性水溶液のままで、次の段階のアシル化反応に供することができ、目的のレバミピドが高収率で得ることができるため、本発明は、レバミピドの大量合成に極めて有効である。
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004348425 | 2004-12-01 | ||
PCT/JP2005/022412 WO2006059781A1 (en) | 2004-12-01 | 2005-11-30 | Improved process for preparing rebamipide |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007503476A JP2007503476A (ja) | 2007-02-22 |
JP3911008B2 true JP3911008B2 (ja) | 2007-05-09 |
Family
ID=35788485
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006546720A Active JP3911008B2 (ja) | 2004-12-01 | 2005-11-30 | レバミピドの改良製造法 |
Country Status (7)
Country | Link |
---|---|
US (1) | US7718805B2 (ja) |
JP (1) | JP3911008B2 (ja) |
KR (1) | KR101098116B1 (ja) |
CN (1) | CN100537541C (ja) |
HK (1) | HK1099298A1 (ja) |
IL (1) | IL177039A (ja) |
WO (1) | WO2006059781A1 (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101032600B1 (ko) | 2008-08-11 | 2011-05-06 | 동우신테크 주식회사 | 고순도 레바미피드의 제조방법 |
CN101870674B (zh) * | 2009-04-21 | 2012-04-18 | 陕西大生化学科技有限公司 | 改进的瑞巴派特中间体的制备方法 |
CN102174015B (zh) * | 2011-03-07 | 2013-10-16 | 江西同和药业有限责任公司 | 瑞巴派特的精制方法 |
SA113340675B1 (ar) * | 2012-06-26 | 2015-08-16 | استيش. كو.، ليمتد | أدوية ريباميبايد تحضيرية جديدة، طريقة تحضيرها واستخدامها |
CN103113294B (zh) * | 2013-03-11 | 2016-04-27 | 浙江远力健药业有限责任公司 | 瑞巴派特的合成方法 |
CN104262346B (zh) * | 2014-09-17 | 2016-06-08 | 广东众生药业股份有限公司 | 一种溴芬酸钠二聚体杂质的制备方法 |
WO2016108319A1 (ko) * | 2015-01-02 | 2016-07-07 | 삼진제약 주식회사 | 신규 레바미피드 전구체의 염 및 이의 용도 |
KR20170094584A (ko) * | 2016-02-11 | 2017-08-21 | 삼진제약주식회사 | 레바미피드 전구체를 포함하는 면역질환 및 대사성질환의 예방 또는 치료를 위한 경구투여용 약제학적 조성물 |
CN113248429A (zh) * | 2021-06-01 | 2021-08-13 | 千辉药业(安徽)有限责任公司 | 一种瑞巴派特原料药的制备方法 |
CN115028579B (zh) * | 2022-06-21 | 2023-07-18 | 福建海西新药创制股份有限公司 | 一种瑞巴派特原料药的合成方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4578381A (en) | 1982-07-05 | 1986-03-25 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
JPS6019767A (ja) * | 1983-07-11 | 1985-01-31 | Otsuka Pharmaceut Co Ltd | カルボスチリル誘導体を有効成分とする抗潰瘍剤 |
JP2820739B2 (ja) | 1989-10-28 | 1998-11-05 | 大塚製薬株式会社 | カルボスチリル誘導体の製造法 |
JP3145468B2 (ja) | 1992-02-27 | 2001-03-12 | マニー株式会社 | かしめ装置に於ける下型の取付構造 |
KR100669823B1 (ko) | 2001-02-20 | 2007-01-17 | 경동제약 주식회사 | 2-(4-클로로벤조일아미노)-3-[2(1h)-퀴놀리논-4-일]프로피온산의 제조방법 및 그 중간체 |
KR100766578B1 (ko) | 2001-12-18 | 2007-10-11 | 동화약품공업주식회사 | 레바미피드의 제조방법 |
KR100520184B1 (ko) | 2002-10-11 | 2005-10-10 | 한미약품 주식회사 | 레바미파이드의 개선된 제조방법 |
-
2005
- 2005-11-30 CN CNB2005800057780A patent/CN100537541C/zh not_active Expired - Fee Related
- 2005-11-30 US US10/587,509 patent/US7718805B2/en not_active Expired - Fee Related
- 2005-11-30 JP JP2006546720A patent/JP3911008B2/ja active Active
- 2005-11-30 WO PCT/JP2005/022412 patent/WO2006059781A1/en active Application Filing
- 2005-11-30 KR KR1020067015793A patent/KR101098116B1/ko active IP Right Grant
-
2006
- 2006-07-23 IL IL177039A patent/IL177039A/en not_active IP Right Cessation
-
2007
- 2007-06-15 HK HK07106485.2A patent/HK1099298A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
US7718805B2 (en) | 2010-05-18 |
HK1099298A1 (en) | 2007-08-10 |
US20070249835A1 (en) | 2007-10-25 |
KR101098116B1 (ko) | 2011-12-26 |
IL177039A (en) | 2011-03-31 |
CN100537541C (zh) | 2009-09-09 |
KR20070085057A (ko) | 2007-08-27 |
JP2007503476A (ja) | 2007-02-22 |
IL177039A0 (en) | 2006-12-10 |
CN1922145A (zh) | 2007-02-28 |
WO2006059781A1 (en) | 2006-06-08 |
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