WO1999065902A1 - PROCEDE DE PRODUCTION DE 2,4-DIMETHYLCARBOLINE ET DE 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOL - Google Patents

PROCEDE DE PRODUCTION DE 2,4-DIMETHYLCARBOLINE ET DE 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOL Download PDF

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Publication number
WO1999065902A1
WO1999065902A1 PCT/EP1999/003775 EP9903775W WO9965902A1 WO 1999065902 A1 WO1999065902 A1 WO 1999065902A1 EP 9903775 W EP9903775 W EP 9903775W WO 9965902 A1 WO9965902 A1 WO 9965902A1
Authority
WO
WIPO (PCT)
Prior art keywords
indole
dimethylcarboline
dimethylpyrimido
aminoindole
acetylacetone
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/EP1999/003775
Other languages
German (de)
English (en)
Inventor
Peter Fey
Jan-Bernd Lenfers
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.)
Bayer AG
Original Assignee
Bayer AG
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 Bayer AG filed Critical Bayer AG
Priority to AU45037/99A priority Critical patent/AU4503799A/en
Publication of WO1999065902A1 publication Critical patent/WO1999065902A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • 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

Definitions

  • the present invention relates to a process for the preparation of 2,4-dimethylcarboline and 2,4-dimethylpyrimido [1,2-a] indole.
  • Dimethylcarboline requires two further reaction steps: the reaction of the aminoindole hydrochloride with acetylacetone in pyridine to give 2,4-dimethy! Pyrimido [1,2-a] indole and the subsequent rearrangement by heating 2,4-dimethylpyrimido [1,2- a] indole with a large excess of potassium hydroxide in ethanol [cf. ON. Kost, R.S. Sagitullin, V.l. Gorbunov, N.N. Modyanov; Khim.
  • the present invention solves the above problems by a new method of manufacturing
  • the intermediate 2-aminoindole before reaction with acetylacetone in an amount of more than one, preferably 1.1 to 5, particularly preferably 1.1 to 3 Equivalents of an organic or inorganic acid added.
  • the process according to the invention enables the access of 2,4-dimethylcarboline and 2,4-dimethylpyrimido [1,2-a] indole in an elegant, inexpensive and high-yielding manner.
  • Amounts preferably 0.05 to 0.15 equivalents, particularly preferably 0.11 equivalents of the base sodium methylate are required.
  • the process according to the invention is not only distinguished by very good yields of the desired compounds, but also by its surprisingly simple and ecologically optimal reaction procedure, since the amounts of waste are reduced almost completely.
  • the 2,4-dimethylcarboline is preferably produced in a temperature range from 40 ° C. to 80 ° C., particularly preferably at 80 ° C. and in a protective gas atmosphere.
  • the 2,4-dimethylpyrimido [1,2-a] indole is preferably prepared at room temperature.
  • the reaction can take place at normal pressure, at elevated or low pressure (e.g. in a range from 0.5 to 5 bar). In general, it is preferably carried out at normal pressure.
  • the organic solvent is preferably a basic solvent which is inert towards the reactants; Examples include pyridine and alkyl pyridines such as e.g. Lutidine. Pyridine is particularly preferred.
  • Acids in the context of the invention generally represent hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, methanesulfonic acid, ethanesulfonic acid, trifluoroacetic acid and trichloroacetic acid. Hydrochloric acid and Schwefelklar Preference ⁇ "
  • the reaction is carried out under an N 2 atmosphere.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne un procédé de production de 2,4-diméthylcarboline et de 2,4-diméthylpyrimido[1,2-a]indol, procédé selon lequel on fait réagir du 2-aminophénylacétonitrile avec (A) du méthylate de sodium dans un solvant organique au moyen de la phase intermédiaire de l'amino-indol puis par addition d'acétylacétone, dans le cas de la production de 2,4-diméthylcarboline, ou avec (B) du méthylate de sodium dans un solvant organique au moyen de la phase intermédiaire du 2-amino-indol puis par addition d'acétylacétone, dans le cas de la production de 2,4-diméthylpyrimido[1,2-a]indol, une quantité supérieure à un équivalent d'un acide organique ou inorganique étant ajoutée avant l'addition d'acétylacétone.
PCT/EP1999/003775 1998-06-13 1999-06-01 PROCEDE DE PRODUCTION DE 2,4-DIMETHYLCARBOLINE ET DE 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOL Ceased WO1999065902A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU45037/99A AU4503799A (en) 1998-06-13 1999-06-01 Method for producing 2,4-dimethylcarboline and 2,4-dimethylpyrimido(1,2-a)indole

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1998126469 DE19826469A1 (de) 1998-06-13 1998-06-13 Verfahren zur Herstellung von 2,4-Dimethylcarbolin und 2,4-Dimethylpyrimido[1,2-a]indol
DE19826469.0 1998-06-13

Publications (1)

Publication Number Publication Date
WO1999065902A1 true WO1999065902A1 (fr) 1999-12-23

Family

ID=7870846

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/003775 Ceased WO1999065902A1 (fr) 1998-06-13 1999-06-01 PROCEDE DE PRODUCTION DE 2,4-DIMETHYLCARBOLINE ET DE 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOL

Country Status (3)

Country Link
AU (1) AU4503799A (fr)
DE (1) DE19826469A1 (fr)
WO (1) WO1999065902A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103483339A (zh) * 2013-09-16 2014-01-01 淮阴师范学院 一种9H-吡啶并[2,3-b]吲哚的简易合成方法
CN104774202A (zh) * 2015-04-08 2015-07-15 河南师范大学 一种9H-吡啶并[2,3-b]吲哚类化合物的合成方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0799828A2 (fr) * 1996-04-04 1997-10-08 Bayer Ag Pyrimido [1,2-a] indoles

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0799828A2 (fr) * 1996-04-04 1997-10-08 Bayer Ag Pyrimido [1,2-a] indoles

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 073, no. 11, 14 September 1970, Columbus, Ohio, US; abstract no. 056049, KOST A N ET AL: "Indole chemistry. XI. Synthesis of.alpha.-carbolines and pyrimido[1,2-a]indoles from 2-aminoindoles" XP002116406 *
CHEMICAL ABSTRACTS, vol. 079, no. 21, 26 November 1973, Columbus, Ohio, US; abstract no. 126439, SAGITULLIN R S ET AL: "Indole chemistry. XXXVII. Reaction of 2-aminoindole with.beta.-diketones" XP002116407 *
CHEMICAL ABSTRACTS, vol. 082, no. 7, 17 February 1975, Columbus, Ohio, US; abstract no. 043311, SAGITULLIN R S ET AL: "Rearrangement of pyrimido[1,2-a]indoles to.alpha.-carbolines" XP002116408 *
KHIM. GETEROTSIKL. SOEDIN. (KGSSAQ);1970; (3); PP.359-63, Mosk. Gos. Univ.;Moscow; USSR *
KHIM. GETEROTSIKL. SOEDIN. (KGSSAQ);1973; (8); PP.1043-6, Mosk. Gos. Univ. im. Lomonosova;Mosco; USSR *
KHIM. GETEROTSIKL. SOEDIN. (KGSSAQ);1974; (10); PP.1436, Mosk. Gos. Univ. im. Lomonosova;Moscow; USSR *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103483339A (zh) * 2013-09-16 2014-01-01 淮阴师范学院 一种9H-吡啶并[2,3-b]吲哚的简易合成方法
CN104774202A (zh) * 2015-04-08 2015-07-15 河南师范大学 一种9H-吡啶并[2,3-b]吲哚类化合物的合成方法
CN104774202B (zh) * 2015-04-08 2016-08-31 河南师范大学 一种9H-吡啶并[2,3-b]吲哚类化合物的合成方法

Also Published As

Publication number Publication date
DE19826469A1 (de) 2000-05-25
AU4503799A (en) 2000-01-05

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