KR920014814A - 3-아미노-9,13b-디하이드로-1H-디벤즈[c,f]이미다조[1,5,-a]아제핀-염산염의 제조방법 - Google Patents

3-아미노-9,13b-디하이드로-1H-디벤즈[c,f]이미다조[1,5,-a]아제핀-염산염의 제조방법 Download PDF

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KR920014814A
KR920014814A KR1019920000978A KR920000978A KR920014814A KR 920014814 A KR920014814 A KR 920014814A KR 1019920000978 A KR1019920000978 A KR 1019920000978A KR 920000978 A KR920000978 A KR 920000978A KR 920014814 A KR920014814 A KR 920014814A
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dibenz
dihydro
azepine
hydrochloride
amino
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KR1019920000978A
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KR100196965B1 (ko
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슈나이더 하인리히
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디터 라우딘, 루돌프 호프만
베링거 인겔하임 케이지
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract

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Description

3-아미노-9,13b-디하이드로-1H-디벤즈[c,f]이미다조[1.5-a]아제핀-염산염의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (6)

  1. 6-프탈아미도메틸-5H-디벤즈〔b,e〕아제핀을 수소화시키고, 생성물을 히드라진과 반응시킨 후 브로모시아노겐과 반응시켜서 생성된 염기를 염산염의 형태로 침전시킴을 특징으로 하는, 3-아미노-9,13b-디하이드로-1H-디벤즈〔c,f〕이미다조〔1,5-a〕아제핀-염산염의 제조방법.
  2. 제 1항에 있어서, 6-프탈아미도메틸-5H-디벤즈〔b,e〕아제핀의 수소화를 디메틸포름아미드중에서 1 내지 10바, 바람직하게는 6 내지 8바 및 특히 더 바람직하게는 7바의 수소압 및 40 내지 100℃, 바람직하게는 60내지 80℃, 특히 더 바람직하게는 70℃의 온도에서 촉매로서 pd/c를 사용하고 포름산을 0.5내지 5mol/mol, 바람직하게는 2mol/mol 농도로 첨가하여 수행함을 특징으로 하는 방법.
  3. 제 1항에 있어서, 6-(프탈아미도메틸)-6,11-디하이드로-5H-디벤즈〔b,e〕아제핀의 가히드라진분해 반응을 알카리 용액 중에서 수행함을 특징으로 하는 방법.
  4. 제 1항에 있어서, a) 알카리 용액 중에서 액 100 내지 150℃, 바람직하게는 110 내지 120℃에서 히드라진 수화물과 반응시키고, b) 사용되는 염기는 알카리 금속 수산화물 용액, 바람직하게는 수산화나트륨 용액 이며, c) 고비점의 수혼화성 용매, 바람직하게는 에틸렌글리콜, 프로필렌글리콜, 글리세롤, 보다 특히 에틸렌글리콜중에서 후처리하고, d) 가히드라지분해 생성물을 분리하기 위해, 염소화된 탄화수소, 바람직하게는 클로로포름, 사염화탄소, 1,2-디클로로 에탄, 더 특히 디클로메탄으로 추출함을 특징으로하여, 6-(프탈아미도메틸)-6,11-디하이드로-5H-디베즈〔b,e〕아제핀을 가히드라진분해시키는 방법.
  5. 제 1항에 있어서, a) 브롬화나트륨 수용액을 5 내지 25℃, 바람직하게는 10 내지 15℃에서 브롬과 반응시킨 다음 10 내지 15℃에서 시안화나트륨과 반응시키고, b) 이용액을 5 내지 35℃, 바람직하게는 15 내지 25℃에서 가히드라진분해 생성물을 함유하는 추출 상과 함게 교반시키고, c) 염기, 바람직하게는 N,N-디벤질아민, N,N-디부틸아민, 디에탄올아민, 디이소프로필아민, N-에틸벤질아민, 살코신-Na 염 및 특히 N-메틸벤질아민을 가하고, d) 생성된 3-아미노-9,13b-디하이드로-1H-디벤즈〔c,f]-이미다조〔1,5-a〕아제핀을 벤젠, 크실렌 또는 할로벤젠, 바람직하게는 톨루엔 중에 용해시키고 수산화나트륨 용액을 가하여 침전시킴을 특징으로하여, 6-아미노메틸-6,11-디하이드로-5H-디벤즈〔b,e〕아제핀과 브로모시아노겐을 반응시키는 방법.
  6. 제 1항에 있어서, 염기를, 용해된 염산 가스를 0.2 내지 7.0중량%, 바람직하게는 4.7중량%의 농도로 함유한 디메틸포름아미드중에서 가열하에 용해시킨후 여과하고 용액의 약⅓을 증류시키고, 혼합믈을 냉각시켜 3-아미노-9,13b-디하이드로-1H-디벤즈〔c,f〕이미다졸〔1,5-a〕아제핀-염산염을 침전시킴을 특징으로 하여, 염산염을 제조하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019920000978A 1991-01-25 1992-01-24 3-아미노-9,13b-디하이드로-1h-디벤즈(c,f)이미다조(1,5,-a) 아제핀-염산염의 제조방법 KR100196965B1 (ko)

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DE4102148A DE4102148A1 (de) 1991-01-25 1991-01-25 Verfahren zur herstellung von 3-amino-9,13b-dihydro-1h-dibenz-(c,f)imidazol(1,5-a)azepin-hydrochlorid
DEP4102148.7 1991-01-25

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KR100196965B1 KR100196965B1 (ko) 1999-06-15

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US (1) US5312916A (ko)
EP (1) EP0496306B1 (ko)
JP (1) JP3133448B2 (ko)
KR (1) KR100196965B1 (ko)
AT (1) ATE127802T1 (ko)
DE (2) DE4102148A1 (ko)
DK (1) DK0496306T3 (ko)
ES (1) ES2078559T3 (ko)
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JP2001131177A (ja) * 1999-11-08 2001-05-15 Ohara Yakuhin Kogyo Kk ジベンズ［ｃ，ｆ］イミダゾ［１，５−ａ］アゼピンの製造方法及びその製造中間体
DE19954516A1 (de) * 1999-11-12 2001-05-17 Boehringer Ingelheim Int Epinastin-haltige Lösungen
DE19958460A1 (de) * 1999-12-03 2001-06-07 Boehringer Ingelheim Pharma Verfahren zur Herstellung von Epinastine-Hydrochlorid in der hochschmelzenden Kristallmodifikation
KR100392692B1 (ko) * 2001-05-31 2003-07-28 바이오네스트 주식회사 에피나스틴 및 그 약제학적으로 허용되는 염의 새로운제조방법
JP4298212B2 (ja) * 2002-03-29 2009-07-15 大日本印刷株式会社 塩酸エピナスチン高融点型結晶の製造法
CN100341857C (zh) * 2002-04-11 2007-10-10 柯尼卡美能达化学株式会社 6－氨甲基－6,11－二氢－5H－二苯并[b,e]氮杂䓬的制造方法
JP4514017B2 (ja) * 2003-03-27 2010-07-28 大日本印刷株式会社 塩酸エピナスチンの製造方法
KR101386530B1 (ko) 2006-12-29 2014-04-18 케이피엑스 라이프사이언스 주식회사 순도 및 수율이 향상된3-아미노-9,13ｂ디하이드로-1Ｈ-디벤즈-[ｃ,ｆ]이미다조[1,5-ａ]-아제핀 염산염의 제조방법
CN101130544B (zh) * 2007-09-26 2010-09-08 杭州龙山化工有限公司 依匹斯汀的化学合成方法
KR100909295B1 (ko) * 2007-11-15 2009-07-24 주식회사 참조아 6-아미노메틸- 6,11-디하이드로-5Ｈ-디벤즈[ｂ,ｅ]아제핀의 제조방법
JP2009102434A (ja) * 2009-02-09 2009-05-14 Dainippon Printing Co Ltd ６−アミノメチル−６，１１−ジヒドロ−５Ｈ−ジベンズ［ｂ，ｅ］アゼピンの製造方法
JP2010120960A (ja) * 2010-02-17 2010-06-03 Dainippon Printing Co Ltd 塩酸エピナスチンの製造方法
CN104098575B (zh) * 2013-04-15 2016-06-01 四川科瑞德凯华制药有限公司 一种盐酸依匹斯汀晶型及其制备方法和用途
CN104447757B (zh) * 2014-11-17 2017-03-22 合肥华方医药科技有限公司 依匹斯汀的合成方法
CN105153169B (zh) * 2014-11-27 2018-11-30 兆科药业（广州）有限公司 一种盐酸依匹斯汀的合成方法
CN107118216B (zh) * 2017-05-08 2019-03-08 宏冠生物药业有限公司 一种盐酸依匹斯汀杂质b的合成方法
CN107141297B (zh) * 2017-06-23 2019-07-02 合肥华方医药科技有限公司 一种盐酸依匹斯汀的合成方法
KR102080239B1 (ko) 2019-08-06 2020-02-21 한양대학교 에리카산학협력단 에피나스틴의 신규 제조방법
CN112028897A (zh) * 2020-11-06 2020-12-04 南京远淑医药科技有限公司 一种盐酸依匹斯汀的合成方法

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EP0496306A1 (de) 1992-07-29
DE59203611D1 (de) 1995-10-19
EP0496306B1 (de) 1995-09-13
KR100196965B1 (ko) 1999-06-15
DK0496306T3 (da) 1996-01-22
ES2078559T3 (es) 1995-12-16
JPH04346988A (ja) 1992-12-02
ATE127802T1 (de) 1995-09-15
US5312916A (en) 1994-05-17
GR3017693T3 (en) 1996-01-31
JP3133448B2 (ja) 2001-02-05
DE4102148A1 (de) 1992-07-30

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