WO2019008594A1 - Procédé continu pour la préparation de 2-(1h-imidazol-4-yl) éthanamine et de ses sels pharmaceutiquement acceptables - Google Patents

Procédé continu pour la préparation de 2-(1h-imidazol-4-yl) éthanamine et de ses sels pharmaceutiquement acceptables Download PDF

Info

Publication number
WO2019008594A1
WO2019008594A1 PCT/IN2017/050610 IN2017050610W WO2019008594A1 WO 2019008594 A1 WO2019008594 A1 WO 2019008594A1 IN 2017050610 W IN2017050610 W IN 2017050610W WO 2019008594 A1 WO2019008594 A1 WO 2019008594A1
Authority
WO
WIPO (PCT)
Prior art keywords
histamine
process according
pharmaceutically acceptable
acceptable salts
preparation
Prior art date
Application number
PCT/IN2017/050610
Other languages
English (en)
Inventor
Sanjeev Kumar
Rajesh Kumar
Brijesh Kumar Shukla
Rajendra Singh SHEKHAWAT
Sujay Biswas
Dharam Vir
Original Assignee
Jubilant Generics Limited
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 Jubilant Generics Limited filed Critical Jubilant Generics Limited
Publication of WO2019008594A1 publication Critical patent/WO2019008594A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine

Definitions

  • the present invention discloses a commercially viable, cost effective and energy efficient process for the preparation of 2-(lH-Imidazol-4-yl) ethanamine or pharmaceutically acceptable salts thereof in high purity and yield via application of continuous flow technology.
  • 2-(lH-Imidazol-4-yl) ethanamine represented as compound of formula I, possesses significant biological activity and is used as standard in biological assays and as a component in certain allergy diagnostic kits. Histamine occurs widely in nature, but to take full advantage of its therapeutic properties, it is important to obtain large quantities of histamine of pharmaceutical grade by synthetic routes.
  • Histamine in therapeutic applications is used as its dihydrochloride salt, which can be conveniently synthesized by decarboxylation of histidine. Using this synthetic process, histidine is decarboxylated and subsequently treated to form the dihydrochloride salt form of the molecule.
  • Hashimoto et al in Chemistry Letters, 1986, 883-896 discussed the preparation of histamine, wherein histidine is decarboxylated using cyclohexanone as a catalyst in cyclohexanol solvent.
  • the process disclosed involves the decarboxylation reaction being carried out in 26 hours and used toluene and HC1 gas for the preparation of dihydrochloride salt.
  • the process disclosed is not industrially feasible as the reaction time is too long, which results in a lot of energy consumption and further the process fails in providing histamine dihydrochloride of pharmaceutical grade as it contains a number of impurities which makes the process unsuitable for large scale production.
  • JPH05255204 discloses use of acetophenone catalyst and diethylene glycol as solvent for the decarboxylation of histidine to histamine.
  • the said process is also reported to be inconsistent in providing histamine dihydrochloride in desired purity and yield.
  • the process disclosed suffered the incompatibility in terms of removal of traces of diethylene glycol as histamine and its dihydrochloride salt are highly soluble in water and none of the isolation techniques worked efficiently to remove the diethylene glycol solvent from the product.
  • it is rendered inapplicable on industrial scale.
  • the principal object of the present invention is to provide an improved and efficient process for the preparation of histamine or pharmaceutically acceptable salts thereof which is simple, economic and alleviates one or more problems of the prior art disclosed processes.
  • the present invention provide a process for the preparation of histamine or pharmaceutically acceptable salts thereof, comprising
  • step (b) performing the decarboxylation reaction by feeding solution of step (a) to a continuous reactor to obtain histamine and optionally converting the histamine to its pharmaceutically acceptable salts.
  • Chemical reactors are vessels, wherein chemical reactions are carried out; their performance determines the reliability and suitability of a process, its environment safety, the consumption of energy and the raw materials required.
  • a continuous reactor is a reactor where there are no moving parts other than pumps that deliver the reactants. To achieve efficient mixing of reactants the addition of static mixing elements such as glass beads inside the reactor is done that provides ideal conditions of radial mixing and continuous flow necessary to perform reactions.
  • One such example of a continuous reactor is plug flow reactor. In a plug flow reactor, the flow of reactants pumped in the reactor is laminar and the properties of the reaction medium i.e. pressure, temperature, reactant and product concentrations are the same throughout the entire cross section of flow.
  • Plug flow reactors usually operate in adiabatic and non-isothermal conditions. Consequently, from the standpoint of kinetic parameters of a chemical reaction under isothermal conditions, plug flow reactors are more efficient than stirred tank reactors.
  • the present invention provides an improved method for the preparation of histamine or pharmaceutically acceptable salts thereof using a continuous reactor.
  • the process has distinct advantages in regard to cycle time, energy consumption, yield and product purity over traditional methods.
  • the process employs application of continuous reactor technology for the preparation of desired product in high yield and high purity with enhanced in-process control on impurities with shorter reaction time.
  • the present invention provides a process for the preparation of histamine or pharmaceutically acceptable salts thereof, comprising
  • a solution of L-histidine is prepared using a solvent and a catalyst.
  • the solvent used is selected from the group comprising of alcohols such as ethylene glycol and the like; aromatic hydrocarbon such as toluene, xylene and the like; aprotic polar solvents such as N-methyl pyrrolidone, N,N-dimethylformamide, dimethylsulphoxide and the like; water or mixtures thereof.
  • the catalyst used is selected from the group comprising of acetophenone, 4-methylacetophenone, 4-nitroacetophenone, 4-bromoacetophenone, benzoyl peroxide, 2,2'-azobisisobutyronitrile, cyclohexanone and the like.
  • the solution of L-histidine and the catalyst is prepared at room temperature.
  • the catalyst is used in 0.5 to 1.5 mole equivalents of L-histidine.
  • the decarboxylation reaction of L-histidine is carried out by feeding the solution prepared in step (a) at the flow rate of 20-80 ml/min at reflux temperature to a continuous reactor.
  • the continuous reactor used is selected from the group comprising of plug flow reactor and the like.
  • the reaction is optionally carried out under inert atmosphere or under an inert gas stream at reflux temperature of the solvent of the solution. Examples of the inert gas include nitrogen, helium, neon, argon and the like.
  • the residence time necessary in the method according to the invention depends on various parameters, such as, for example, the temperature or reactivity of the starting materials.
  • the term "residence time" refers to the internal volume of the reaction zone within the continuous reactor occupied by the reactant fluid flowing through the space, at the temperature and pressure being used.
  • the residence time is between about 1 minute and about 10 minutes.
  • the resulting reaction mixture is subjected to various isolation techniques to isolate histamine such as extraction, filtration, distillation etc.
  • histamine obtained is optionally converted to its pharmaceutically acceptable salts selected from the group comprising of hydrochloride, hydrobromide, tartrate, oxalate and the like.
  • the final product is optionally purified by a suitable recrystallization procedure known in the literature.
  • the histamine hydrochloride obtained is having purity not less than 99 %.
  • Example 2 Purification of histamine dihydrochloride: To histamine hydrochloride (100 g), added methanol (800 ml) and raised the temperature of reaction mass to 60-70 °C and stirred to get a clear solution. To the clear solution added carbon (5 g) at 50-55 °C and stirred for another 30 minutes. The solution was filtered and the solvent was partially distilled out. The resulting reaction mass, added isopropyl alcohol (300 ml) and raised the temperature of reaction mass to 60-70 deg C, stirred at this temperature for about 1 hour. The reaction mass was cooled slowly to 10-15 °C while stirring. The solid so obtained was filtered and dried to obtain histamine dihydrochloride .

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé commercialement viable, rentable et énergétiquement efficace pour la préparation de 2-(1H-imidazol-4-yl) éthanamine ou de ses sels pharmaceutiquement acceptables avec une pureté élevée et un haut rendement par l'application d'une technologie d'écoulement continu.
PCT/IN2017/050610 2017-07-03 2017-12-22 Procédé continu pour la préparation de 2-(1h-imidazol-4-yl) éthanamine et de ses sels pharmaceutiquement acceptables WO2019008594A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201711023282 2017-07-03
IN201711023282 2017-07-03

Publications (1)

Publication Number Publication Date
WO2019008594A1 true WO2019008594A1 (fr) 2019-01-10

Family

ID=64949827

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2017/050610 WO2019008594A1 (fr) 2017-07-03 2017-12-22 Procédé continu pour la préparation de 2-(1h-imidazol-4-yl) éthanamine et de ses sels pharmaceutiquement acceptables

Country Status (1)

Country Link
WO (1) WO2019008594A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113045500A (zh) * 2021-03-31 2021-06-29 苏州园方生物科技有限公司 一种组胺二盐酸盐的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6403806B1 (en) * 1998-12-23 2002-06-11 Maxim Pharmaceuticals, Inc. Synthesis of histamine dihydrochloride
US7485756B2 (en) * 2006-12-20 2009-02-03 Evonik Degussa Gmbh Continuous process for decarboxylating carboxylic acids

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6403806B1 (en) * 1998-12-23 2002-06-11 Maxim Pharmaceuticals, Inc. Synthesis of histamine dihydrochloride
US7485756B2 (en) * 2006-12-20 2009-02-03 Evonik Degussa Gmbh Continuous process for decarboxylating carboxylic acids

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113045500A (zh) * 2021-03-31 2021-06-29 苏州园方生物科技有限公司 一种组胺二盐酸盐的制备方法

Similar Documents

Publication Publication Date Title
CN110615744A (zh) 一种布瓦西坦中间体及其制备方法
CN107848943A (zh) 制备色满酮衍生物的新方法
WO2019008594A1 (fr) Procédé continu pour la préparation de 2-(1h-imidazol-4-yl) éthanamine et de ses sels pharmaceutiquement acceptables
CN110845443B (zh) 一种制备高纯度盐酸托哌酮的方法
CN112739675B (zh) 回收高品质3-甲基-丁-3-烯-1-醇的方法
KR20220101115A (ko) 하이드록삼산의 합성을 위한 연속 유동 프로세스
CN109574797B (zh) 一种手性苄醇的制备方法
CN108164423B (zh) 一种盐酸萘替芬的制备方法
US10889549B2 (en) Continuous process for the preparation of 2-(1H-imidazol-4-yl) ethanamine and pharmaceutically acceptable salts thereof
JP6676146B2 (ja) クロマノール誘導体の新規な製造方法
AU2021404731B2 (en) Synthesis method for cyclopropyl-containing chiral amine hydrochloride
CN112645813B (zh) 一种(r)-3-环己烯甲酸的制备方法
EP3896057B1 (fr) Procédé de préparation en continu de citalopram diol
CN109824539B (zh) 一种由去甲基金霉素合成替加环素的新方法
WO2022011948A1 (fr) Procédé de préparation de vortioxétine
CN112538074A (zh) 一种溴莫尼定脱溴杂质的制备方法
CN108101845B (zh) 一种艾曲泊帕的制备方法
US20220033344A1 (en) Method for preparing (2s,3s)-3-amino-bicyclo[2.2.2]octane-2-carboxylate
CN112625015B (zh) 一种2-（1,3-二氢-2-异苯并呋喃）-1-苯乙酮化合物的制备方法
CN115724728B (zh) 1,7-二氯-4-庚酮的合成工艺
CN115572263B (zh) 一种肼盐催化酮连氮环化合成吡唑啉的方法
CN114853619B (zh) 一种适于工业化生产的n-甲基酪胺盐酸盐的制备方法
CN112300150B (zh) 一种马罗匹坦及其中间体的制备方法
CN107445850B (zh) 一种12-氨基十二酸的制备方法
CN114014819A (zh) 一种1,4,8,11－四氮杂环十四烷的制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17916608

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 17916608

Country of ref document: EP

Kind code of ref document: A1