CAS: 59467-94-6; (Z)-But-2-Enedioic Acid,8-Chloro-6-(2-Fluorophenyl)-1-Methyl-4H-Imidazo[1,5-A][1,4]Benzodiazepine

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CAS号110-16-7 马来酸 | CAS号59467-70-8 咪唑安定 | CAS号59468-44-9 8-氯-6-(2-氟苯基)-1...

合成工艺路线路线简述

    📜5-(Aminomethyl)-1-{4-Chloro-2-[(2-Fluorophenyl)Carbonyl]Phenyl}-2-Methyl-1H-Imidazole-4-Carboxylic Acid Disulfate 以 N-甲基吡咯烷酮,乙醇 作为反应溶剂,化学反应 0.5H,反应生成 马来酸咪达唑仑
    参考文献:Process For The Synthesis Of 4H-Imidazo [1,5-A] [1,4] Benzodiazepines,In Particular Midazolam And Salts Thereof
    标题:Process For The Synthesis Of 4H-Imidazo [1,5-A] [1,4] Benzodiazepines,In Particular Midazolam And Salts Thereof
    摘要:本发明涉及一种制备4H-咪唑[1,5-A][1,4]苯二氮䓬酮,特别是米达唑的过程,通过对公式(II)的5-氨基甲基-1-苯基-1H-咪唑-4-羧酸衍生物的有效和选择性脱羧反应,避免形成6H-咪唑[1,5-A][1,4]苯二氮䓬酮副产物,并随后进行4H-咪唑[1,5-A][1,4]苯二氮䓬酮产物的异构化过程.

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    专利信息


    专利号:US-8557981-B2
    优先权日:2010-05-04
    标题:Process for the synthesis of 4H-imidazo [1,5-a] [1,4] benzodiazepines, in particular midazolam and salts thereof
    发明人：CASTELLIN ANDREA; MAGGINI MICHELE; DONNOLA PAOLA
    权利人:CASTELLIN ANDREA; MAGGINI MICHELE; DONNOLA PAOLA; ITALIANA SINT SPA
    摘要:The present invention refers to a process for the preparation of 4H-imidazo[1,5-a][1,4]benzodiazepines, in particular Midazolam, through an efficient and selective decarboxylation reaction of the derivative compound of the 5-aminomethyl-1-phenyl-1H-imidazole-4-carboxylic acid of formula (II) n navoiding the formation of the 6H-imidazo[1,5-a][1,4]benzodiazepines by-products and the ensuing process for the isomerization of a 4H-imidazo[1,5-a][1,4]benzodiazepine product.

    专利号:US-2011275799-A1
    优先权日:2010-05-04
    标题:PROCESS FOR THE SYNTHESIS OF 4H-IMIDAZO [1,5-a] [1,4] BENZODIAZEPINES, IN PARTICULAR MIDAZOLAM AND SALTS THEREOF

    专利号:EP-2397470-B1
    优先权日:2010-05-04
    标题:Process for the synthesis of 4H-imidazo[1,5-a][1,4]benzodiazepines, in particular midazolam and salts thereof

    专利号:IT-MI20100777-A1
    优先权日:2010-05-04
    标 题 :PROCEDURE FOR THE SYNTHESIS OF 4H-IMIDAZO [1,5-A] [1,4] BENZODIAZEPINE, IN PARTICULAR OF MIDAZOLAM.

    专利号:IL-212505-A
    优先权日:2010-05-04
    标题:Process for Synthesis of 4h - Imidazo [5,1– a] [4,1] Benzodiazepines, especially Midazolam and its salts

    专利号:EP-2397470-A1
    优先权日:2010-05-04
    标题 :Process for the synthesis of 4H-imidazo[1,5-a][1,4]benzodiazepines, in particular midazolam and salts thereof

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    合成参考文献


    摘要:Arzneimittel-Forschung. Drug Research., 31(2180), 1981 []
    参考文献:10.1007/bf02246454
    摘要:Lau CE, Ma F, Wang Y, Smith C. Pharmacokinetics and bioavailability of midazolam after intravenous, subcutaneous, intraperitoneal and oral administration under a chronic food-limited regimen: relating DRL performance to pharmacokinetics. Psychopharmacology (Berl). 1996 Aug;126(3):241–8. doi: 10.1007/bf02246454.
    参考文献:10.1007/bf00310626
    摘要:Stolerman IP, Garcha HS, Rose IC. Midazolam cue in rats: effects of Ro 15-1788 and picrotoxin. Psychopharmacology (Berl). 1986;89(2):183–8. doi: 10.1007/bf00310626.
    参考文献:10.1007/s00213-003-1703-8
    摘要:Cervo L, Cocco A, Carnovali F. Effects on cocaine and food self-administration of (+)-HA-966, a partial agonist at the glycine/NMDA modulatory site, in rats. Psychopharmacology (Berl). 2004 Apr;173(1-2):124–31. doi: 10.1007/s00213-003-1703-8.
    参考文献:10.1007/s00213-004-1987-3
    摘要:Gourley SL, Debold JF, Yin W, Cook J, Miczek KA. Benzodiazepines and heightened aggressive behavior in rats: reduction by GABA(A)/alpha(1) receptor antagonists. Psychopharmacology (Berl). 2005 Mar;178(2-3):232–40. doi: 10.1007/s00213-004-1987-3.
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