WO2007101536A1 - Verfahren zur herstellung von 1-formamido-3,5-dimethyladamantan - Google Patents

Verfahren zur herstellung von 1-formamido-3,5-dimethyladamantan Download PDF

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Publication number
WO2007101536A1
WO2007101536A1 PCT/EP2007/001433 EP2007001433W WO2007101536A1 WO 2007101536 A1 WO2007101536 A1 WO 2007101536A1 EP 2007001433 W EP2007001433 W EP 2007001433W WO 2007101536 A1 WO2007101536 A1 WO 2007101536A1
Authority
WO
WIPO (PCT)
Prior art keywords
dimethyladamantane
formamido
acid
formamide
formamidation
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP2007/001433
Other languages
German (de)
English (en)
French (fr)
Inventor
Peter R. Schreiner
Andrey A. Fokin
Lukas Wanka
Derek M. Wolfe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Justus Liebig Universitaet Giessen
Merz Pharma GmbH and Co KGaA
Original Assignee
Justus Liebig Universitaet Giessen
Merz Pharma GmbH and Co KGaA
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 Justus Liebig Universitaet Giessen, Merz Pharma GmbH and Co KGaA filed Critical Justus Liebig Universitaet Giessen
Priority to ES07722859T priority Critical patent/ES2392550T3/es
Priority to JP2008556686A priority patent/JP5345403B2/ja
Priority to US12/224,575 priority patent/US8138375B2/en
Priority to EP07722859A priority patent/EP1989175B1/de
Publication of WO2007101536A1 publication Critical patent/WO2007101536A1/de
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/56—Ring systems containing bridged rings
    • C07C2603/58—Ring systems containing bridged rings containing three rings
    • C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
    • C07C2603/74—Adamantanes

Definitions

  • the invention relates to a process for the preparation of 1-formamido-3,5-dimethyladamantane, which is an important intermediate for the production of the used against Alzheimer's disease 1-amino-3,5-dimethyl-adamantane, which is under the active name Memantine is known. It is (and many non-European countries) marketed in Europe under the brand names A- xura ® and Ebixa ® and in the USA under Namenda®.
  • the 1-amino-3,5-dimethyladamantane has long been known as a substance from DE 2 318 461 A1. Its use for the prevention and treatment of cerebral ischemia is described in EP 0 392 059 B1. Accordingly, the synthesis of the 1-formamido-3,5-dimethyladanantane used for its production is hitherto carried out by halogenation of the 1,3-dimethyladamantane with subsequent formamidation. Thereafter, the 1-formamido-3,5-dimethyladamantane is hydrolyzed to the amine with dilute hydrochloric acid.
  • the reaction is generally carried out at -40 0 C to 50 0 C, but preferably at 0 0 C. In the process according to the invention mostly yields of 40-95% are achieved.
  • This process is not only characterized by its freedom from halogen, but also has a more favorable impurity profile, since it proceeds in high yields and with only a small amount of by-products, tolerating even impurities in the starting materials. According to GC-MS, only unreacted starting material and 3,5-dimethyladamantan-1-ol could be detected as by-products during formamidation.
  • the process according to the invention for the synthesis of 1-formamido-3,5-dimethyladamantane permits milder reaction conditions while completely avoiding the use of oleum or 100% nitric acid.
  • the nucleophile used is formamide, the reaction product being 1-formamido-3,5-dimethyladamantane, which can be hydrolyzed with respect to other amides under significantly milder conditions.
  • 1-acetamido-3,5-dimethyladamantane is cleaved by heating NaOH in aqueous or alcoholic base or concentrated hydrochloric acid (36-37% strength) for several hours to give the free 1-amino-3,5-dimethyladamantane, whereas the cleavage of the Formamide already with dilute hydrochloric acid within two hours at 100 0 C succeed.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/EP2007/001433 2006-03-01 2007-02-20 Verfahren zur herstellung von 1-formamido-3,5-dimethyladamantan Ceased WO2007101536A1 (de)

Priority Applications (4)

Application Number Priority Date Filing Date Title
ES07722859T ES2392550T3 (es) 2006-03-01 2007-02-20 Procedimiento para la producción de 1-formamido-3,5-dimetiladamantano
JP2008556686A JP5345403B2 (ja) 2006-03-01 2007-02-20 １−ホルムアミド−３，５−ジメチルアダマンタンの製造方法
US12/224,575 US8138375B2 (en) 2006-03-01 2007-02-20 Method for producing 1-formamido-3,5-dimethyladamantane
EP07722859A EP1989175B1 (de) 2006-03-01 2007-02-20 Verfahren zur herstellung von 1-formamido-3,5-dimethyladamantan

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006009279A DE102006009279A1 (de) 2006-03-01 2006-03-01 Verfahren zur Herstellung von 1-Formamido-3,5-dimethyladamantan
DE102006009279.1 2006-03-01

Publications (1)

Publication Number Publication Date
WO2007101536A1 true WO2007101536A1 (de) 2007-09-13

Family

ID=38197988

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/001433 Ceased WO2007101536A1 (de) 2006-03-01 2007-02-20 Verfahren zur herstellung von 1-formamido-3,5-dimethyladamantan

Country Status (7)

Country Link
US (1) US8138375B2 (enExample)
EP (1) EP1989175B1 (enExample)
JP (1) JP5345403B2 (enExample)
DE (1) DE102006009279A1 (enExample)
ES (1) ES2392550T3 (enExample)
RU (1) RU2455281C2 (enExample)
WO (1) WO2007101536A1 (enExample)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2103597A1 (en) 2008-03-20 2009-09-23 Merz Pharma GmbH & Co.KGaA Process for the manufacture of memantine and intermediate product
WO2009115334A3 (en) * 2008-03-20 2009-11-19 Merz Pharma Gmbh & Co. Kgaa Process for the manufacture of memantine and intermediate product
WO2010069555A1 (en) 2008-12-17 2010-06-24 Merz Pharma Gmbh & Co. Kgaa Method for producing memantine
WO2010083996A1 (en) * 2009-01-21 2010-07-29 Merz Pharma Gmbh & Co. Kgaa A process for preparing memantine

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5778148B2 (ja) 2009-08-04 2015-09-16 メルク パテント ゲーエムベーハー 多環式炭水化物を含む電子デバイス
JP2013180983A (ja) * 2012-03-01 2013-09-12 Tokyo Univ Of Agriculture & Technology Ｎ置換アミド化合物の製造方法
RU2549901C1 (ru) * 2013-12-30 2015-05-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Кубанский государственный университет" (ФГБОУ ВПО "КубГУ") Способ получения n-адамантилированных амидов
EP4005565A1 (en) 2020-11-30 2022-06-01 Merz Pharmaceuticals GmbH Novel uses of adamantane derivatives

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566075A (zh) * 2003-07-01 2005-01-19 北京德众万全药物技术开发有限公司 一种取代的金刚烷胺类化合物或其盐的制备方法
WO2006010362A1 (de) * 2004-07-23 2006-02-02 Justus-Liebig-Universität Giessen Aminoadamantan-derivate, verfahren zu ihrer herstellung und ihre verwendung

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2318461A1 (de) 1973-04-12 1974-10-31 Merz & Co Verfahren zur herstellung von 1,3,5trisubstituierten adamanta-verbindungen
JPS63159330A (ja) * 1986-12-23 1988-07-02 Kawasaki Steel Corp １，３−ジメチルアダマンタンの製造方法
JPS63295519A (ja) * 1987-05-27 1988-12-01 Kawasaki Steel Corp １，３−ジメチルアダマンタンの製造方法
SU1643528A1 (ru) * 1988-10-03 1991-04-23 Научно-производственное объединение "Комплекс" Способ получени 1-ацетаминоадамантана
DE10299048I2 (de) 1989-04-14 2006-07-13 Merz Pharma Gmbh & Co Kgaa Verwendung von Adamantan-Derivaten zur Pr{vention und Behandlung der cerebralen Isch{mie
US5117056A (en) 1990-12-21 1992-05-26 Air Products And Chemicals, Inc. Preparation of N-(1-alkoxyalkyl)formamide and bis formamides
RU2246482C2 (ru) * 2002-12-25 2005-02-20 ООО "Циклан" Способ получения гидрохлорида 1-амино-3,5-диметиладамантана

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1566075A (zh) * 2003-07-01 2005-01-19 北京德众万全药物技术开发有限公司 一种取代的金刚烷胺类化合物或其盐的制备方法
WO2006010362A1 (de) * 2004-07-23 2006-02-02 Justus-Liebig-Universität Giessen Aminoadamantan-derivate, verfahren zu ihrer herstellung und ihre verwendung

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; 19 October 2005 (2005-10-19), XIAOJUN ZHANG: "Preparation of a Substituted Symmetry Adamantane Amine Derivatives", XP002441200, Database accession no. AN:1117324 *
YU. N. KLIMOCHKIN ET AL.: "Synthesis of Alkoxycarbonylaminoadamantanes and Acetylaminoadamantanes in Nitric Acid", BULLETIN OF THE ACADEMY OF SCIENCES OF THE USSR, vol. 37, no. 4, 1988, USSR, pages 757 - 759, XP002441198 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2103597A1 (en) 2008-03-20 2009-09-23 Merz Pharma GmbH & Co.KGaA Process for the manufacture of memantine and intermediate product
WO2009115334A3 (en) * 2008-03-20 2009-11-19 Merz Pharma Gmbh & Co. Kgaa Process for the manufacture of memantine and intermediate product
JP2011514372A (ja) * 2008-03-20 2011-05-06 メルツ・ファルマ・ゲーエムベーハー・ウント・コ・カーゲーアーアー メマンチンの製造方法及び中間生成物
US8436209B2 (en) 2008-03-20 2013-05-07 Merz Pharma Gmbh & Co. Kgaa Process for the manufacture of memantine and intermediate product
WO2010069555A1 (en) 2008-12-17 2010-06-24 Merz Pharma Gmbh & Co. Kgaa Method for producing memantine
WO2010083996A1 (en) * 2009-01-21 2010-07-29 Merz Pharma Gmbh & Co. Kgaa A process for preparing memantine
JP2012513451A (ja) * 2009-01-21 2012-06-14 メルツ・ファルマ・ゲゼルシヤフト・ミト・ベシュレンクテル・ハフツング・ウント・コンパニー・コマンデイトゲゼルシヤフト・アウフ・アクティーン メマンチンの製造方法

Also Published As

Publication number Publication date
JP5345403B2 (ja) 2013-11-20
DE102006009279A1 (de) 2007-09-06
US8138375B2 (en) 2012-03-20
US20090299097A1 (en) 2009-12-03
JP2009528309A (ja) 2009-08-06
RU2455281C2 (ru) 2012-07-10
EP1989175B1 (de) 2012-09-19
RU2008138891A (ru) 2010-04-10
EP1989175A1 (de) 2008-11-12
ES2392550T3 (es) 2012-12-11

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