EP1554255A1 - Procede de production de 2-amino-4-chlor-6-alcoxypyrimidines - Google Patents

Procede de production de 2-amino-4-chlor-6-alcoxypyrimidines

Info

Publication number
EP1554255A1
EP1554255A1 EP03775230A EP03775230A EP1554255A1 EP 1554255 A1 EP1554255 A1 EP 1554255A1 EP 03775230 A EP03775230 A EP 03775230A EP 03775230 A EP03775230 A EP 03775230A EP 1554255 A1 EP1554255 A1 EP 1554255A1
Authority
EP
European Patent Office
Prior art keywords
amino
solvent
mixture
chloro
reaction
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.)
Withdrawn
Application number
EP03775230A
Other languages
German (de)
English (en)
Inventor
Sylvia Huber
Thomas GÜTHNER
Wolfgang Moser
Doris Krammer
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.)
Evonik Operations GmbH
Original Assignee
Degussa GmbH
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 Degussa GmbH filed Critical Degussa GmbH
Publication of EP1554255A1 publication Critical patent/EP1554255A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine

Definitions

  • the present invention relates to a process for the preparation of 2-amino-4-chloro-6-alkoxypyrimidines.
  • ACMP 2-Amino-4-chloro-6-methoxypyrimidine
  • ACMP is also used as an intermediate in active pharmaceutical ingredients; so z. B. in diabetes (cf. WO 01/36 416) or anti-cancer drugs (Zhenghou Daxue, Ziran Kexueban (2000), 32 (2), 87-88).
  • 2-amino-4-chloro-6-ethoxypyrimidine has been described, for example, in connection with the synthesis of herbicides (EP-A 101 308, JP 62111982, Huaxue Shiji (1999) 21 (2), 73-75) and 2 -Amino-4-chloro-6-n-propoxypyrimidine is, for example used as an intermediate in the synthesis of active pharmaceutical ingredients (J. Chem. Med. (1986 19 (5) 676-81).
  • ACMP can also be prepared starting from the N-cyano-cyanoacetimido methyl ester by reaction with a hydrogen halide (cf. JP 01016770). However, the yield in this process is only 60%.
  • the object of the present invention was therefore to provide a process by which 2-amino-4-chloro-6-alkoxypyrimidines can be reacted with an alkali metal alcoholate or a Mixture of alkali metal hydroxides and an alcohol can be prepared without disturbing amounts of 2-amino-4,6-dichloropyrimidine remaining as a starting material in the product.
  • the ADCP and the corresponding alkali alcoholate are used in a preferred molar ratio of 1: 1 to 1.5 and particularly preferably 1: 1.05 to 1.10.
  • Solvent (mixture) carried out, but it is by no means limited to special solvents within this framework. From the series of polar aprotic solvents, those have proven to be particularly suitable which are selected from the group of ketones, amides or nitriles and acetone, methyl ethyl ketone, dimethylimidazolidinone, cyclohexanone, dimethylformamide, N-methylpyrrolidone, acetonitrile and / or their are particularly preferred Mixtures used. Acetone can be regarded as a particularly preferred solvent due to its well-known low toxicity and the simple work-up of the mother liquor formed.
  • reaction at temperatures between 5 and 60 ° C and particularly preferably between 15 and 40 ° C results in a particularly good selectivity of the process according to the invention.
  • the selectivity of the reaction necessary for the product is achieved above all by reaction at low temperatures below about 20 ° C. and a limitation of the alcoholate or the mixture of alkali metal hydroxide / alcohol.
  • 2-Amino-4,6-dichloropyrimidine is generally initially introduced into the solvent and then the alcoholate, for example methylate, or the alkali metal hydroxide and the alcohol, for example methanol, are metered in.
  • the invention provides for the mixture to be heated to a higher temperature after the addition of the reactants, particularly preferably to temperatures between 20 and 60 ° C. and in particular to temperatures between 25 and 45 ° C. If necessary, the reaction can thus be completed after the addition and after-reaction time have ended.
  • the distillate can be recycled without any problems, which advantageously means that the amount of waste generated in the process according to the invention is extremely low.
  • the product is then precipitated according to the present invention by adding water.
  • the water can be added in the form of several portions during the distillation or after the distillation step, which the invention also takes into account.
  • the procedure of adding in portions during the distillation is preferred, since more solvent can be distilled off in this way and higher yields can be achieved as a result.
  • the salt formed in the reaction can either be separated off, for example by filtration from the polar aprotic solvent (acetone) before adding water, and / or the salt can be dissolved in the mother liquor by adding water, which is preferred according to the invention.
  • the product itself is usually isolated by filtration and then dried in vacuo after washing with water.
  • a cleaning step with activated carbon can be carried out according to the invention.
  • the addition takes place after the reaction and preferably before and / or during the distillation and it is preferably additionally stirred for about another hour under the conditions of the after-reaction, that is to say for example at temperatures between 20 and 60 ° C.
  • the activated carbon is then filtered off together with the salt even before the distillation, which advantageously means that all impurities from the raw material, in particular colored compounds or other disruptive by-products, e.g. B.
  • 2-amino-4-chloro-6-alkoxypyrimidines and in particular the ACMP can be obtained in a particularly economical and environmentally friendly manner in high yields and with a very pronounced purity.
  • the present invention relates to a process for the preparation of 2-amino-4-chloro-6-alkoxypyrimidines by reacting the 2-amino-4,6-dichloropyrimidine with an alkali metal alcoholate or a mixture of alkali metal hydroxides and an alcohol, in which the reaction in a polar aprotic solvent (mixture) is carried out, then the solvent is distilled off to> 30% and the product is precipitated by adding water during or after the distillation.
  • a polar aprotic solvent mixture
  • Processes in which acetone, in particular, is used as the polar aprotic solvent and which can be carried out at temperatures between 5 and 60 ° C. can be 2-amino-4-chloro-6-alkoxypyrimidines and especially 2-amino-4-chlorine -6-Methoxypyrimidine in a particularly economical and environmentally friendly manner in high yields and at the same time very distinctive purity.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un procédé de production de 2-amino-4-chlor-6-alcoxypyrimidines. Ce procédé consiste : à faire réagir le composé 2-amino-4,6-dichlorpyrimidine avec un alcoolat alcalin ou un mélange contenant des hydroxydes alcalins et un alcool, dans un (mélange) solvant aprotique polaire ; à éliminer une quantité > 30 % du solvant par distillation ; et à précipiter le produit, par addition d'eau pendant ou après le processus de distillation. Le procédé selon l'invention utilise en particulier de l'acétone en tant que solvant aprotique polaire, se déroule à des températures comprises entre 5 et 60 DEG C et permet de produire des 2-amino-4-chlor-6-alcoxypyrimidines et avant tout le composé 2-amino-4-chlor-6-méthoxypyrimidine à des rendements élevés, de manière particulièrement peu onéreuse et écologique et avec un degré de pureté très élevé.
EP03775230A 2002-10-26 2003-10-24 Procede de production de 2-amino-4-chlor-6-alcoxypyrimidines Withdrawn EP1554255A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10249946A DE10249946B4 (de) 2002-10-26 2002-10-26 Verfahren zur Herstellung von 2-Amino-4-chlor-6-alkoxypyrimidinen
DE10249946 2002-10-26
PCT/EP2003/011844 WO2004037795A1 (fr) 2002-10-26 2003-10-24 Procede de production de 2-amino-4-chlor-6-alcoxypyrimidines

Publications (1)

Publication Number Publication Date
EP1554255A1 true EP1554255A1 (fr) 2005-07-20

Family

ID=32114871

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03775230A Withdrawn EP1554255A1 (fr) 2002-10-26 2003-10-24 Procede de production de 2-amino-4-chlor-6-alcoxypyrimidines

Country Status (5)

Country Link
US (1) US20060035913A1 (fr)
EP (1) EP1554255A1 (fr)
JP (1) JP2006512305A (fr)
DE (1) DE10249946B4 (fr)
WO (1) WO2004037795A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE407931T1 (de) * 2006-06-26 2008-09-15 Chemagis Ltd Verbessertes verfahren zur herstellung von moxonidine
CN102603651A (zh) * 2012-02-27 2012-07-25 安徽丰乐农化有限责任公司 一种高纯农药中间体的合成新工艺
DE102012215896A1 (de) 2012-09-07 2014-03-13 Wörwag Pharma GmbH & Co.KG Moxonidinsynthese mit Hilfe organischer Basen
CN105294572A (zh) * 2015-10-13 2016-02-03 安徽泓德化工技术有限公司 一甲氧基嘧啶胺的制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4199583A (en) * 1970-07-13 1980-04-22 The Upjohn Company Antifungal method, formulations and compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004037795A1 *

Also Published As

Publication number Publication date
JP2006512305A (ja) 2006-04-13
US20060035913A1 (en) 2006-02-16
DE10249946A1 (de) 2004-05-19
WO2004037795A1 (fr) 2004-05-06
DE10249946B4 (de) 2005-06-23

Similar Documents

Publication Publication Date Title
DE69710052T2 (de) Verfahren zur herstellung von zwischenprodukten für pestizide
EP1309562A1 (fr) Esters d'acide 4-alcoxycyclohexan-1-aminocarboxylique, et leur procede de production
EP0201030A2 (fr) Procédé pour la préparation de 1,3,5-triazinetriones
DE10249946B4 (de) Verfahren zur Herstellung von 2-Amino-4-chlor-6-alkoxypyrimidinen
EP0244359B1 (fr) Procédé pour la préparation de dérivés de la pyrimidine
EP0252353B1 (fr) 4-Benzyloxy-3-pyrroline-2-one-1-yl-acétamide, préparation et utilisation
EP0816345B2 (fr) Procédé pour la préparation de 4,6-Dihydroxypyrimidine
DE69623117T2 (de) Verfahren zur herstellung von 4-hydroxy-2-pyrrolidon
EP0378089B1 (fr) Procédé pour la préparation de dérivés de l'amino-2 fluoro-4 pyrimidine
EP0552758A1 (fr) 2,5-Diamino-4,6-dichloropyrimidines N-5-protégées et procédé pour leur préparation
DE10222330A1 (de) Verfahren zur katalysatorfreien Herstellung von Alkoxybenzonitrilen
EP1284261A1 (fr) Procédé de préparation de 4,6-dihydroxypyrimidine
EP1902042B1 (fr) Procede de preparation d'acide 3,4-dichloro-isothiazolcarboxylique
EP0209779A2 (fr) Procédé de préparation de dérivés de 2-cyanamino-pyrimidine
EP1476436B1 (fr) Procede de production de 2-anilino-4,6-dimethylpyrimidine
EP0601353B1 (fr) Procédé pour la préparation de N-(2-sulphatoethyle)pipérazine de pureté elevée
EP0423595B1 (fr) Procédé pour la préparation de 3-trichlorométhyl pyridine
EP0599198A1 (fr) Procédé de préparation de 5-arylhydantoines
DE2443080C3 (de) Verfahren zur Herstellung von ' 2,4-Diamino-5-(3',4'3'-triinethoxybenzyl)-pyrhnidin
DE19640756B4 (de) Verfahren zur Herstellung von 4,6-Dihydroxypyrimidin
EP0973745A1 (fr) Procede de preparation de 2,6-dichloro-5-fluoronicotinonitrile et compose chimique 3-cyano-2-hydroxy-5-fluoropyride-6-one-sel monosodique ainsi que ses tautomeres
DE2942195C2 (fr)
DE2055523C3 (de) 03.07.70 Japan 58217-70 Verfahren zur Herstellung von 2lsopropyl-und2-Phenyl-6-methyl-4(3H)pyrimidon
EP0052225B1 (fr) 2-(2'-(Hydanto-5-yl)-éthyl)-5,5-diméthyl-1,3-dioxanne, procédé pour sa préparation et son application
CH655930A5 (de) Verfahren zur herstellung von 3-hydroxybenzdiazepinonen.

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20050317

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20060124