EP1165512A2 - Procede permettant d'aryler des aza-heterocycles avec des composes aromatiques actives en presence de carbonate de cesium - Google Patents

Procede permettant d'aryler des aza-heterocycles avec des composes aromatiques actives en presence de carbonate de cesium

Info

Publication number
EP1165512A2
EP1165512A2 EP00916872A EP00916872A EP1165512A2 EP 1165512 A2 EP1165512 A2 EP 1165512A2 EP 00916872 A EP00916872 A EP 00916872A EP 00916872 A EP00916872 A EP 00916872A EP 1165512 A2 EP1165512 A2 EP 1165512A2
Authority
EP
European Patent Office
Prior art keywords
group
indole
atoms
aza
general formula
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Withdrawn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
EP00916872A
Other languages
German (de)
English (en)
Inventor
Hubert Barth
Klaus Steiner
Hans-Jürgen BETCHE
Simon Schneider
Ulrich Bayer
Manfred Westermayer
Ulrike Wolfsperger
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.)
Goedecke GmbH
Original Assignee
Goedecke 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 Goedecke GmbH filed Critical Goedecke GmbH
Publication of EP1165512A2 publication Critical patent/EP1165512A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
    • C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
    • C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms

Definitions

  • the invention relates to a method for nucleophilic substitution on activated aromatics of the general formula XIV
  • Rl, R2, R3, R4 and R5 are the same or different and are a hydrogen atom, a nitro group, a cyano group, an alkoxycarbonyl group with up to 5 C atoms, an aldehyde group, an alkylcarbonyl group with up to 5 C atoms, an arylcarbonyl group or mean an amide group, where the radicals Rl to R5 cannot all be a hydrogen atom at the same time and HAL for a halogen atom, but especially a fluorine atom, with nucleophiles such as alcohols, amines, sulfoximides, CH-acidic compounds of the formulas V to XI
  • HETN denotes an aromatic aza heterocycle with a total of 5 or 6 ring atoms, where up to 3 ring atoms can be nitrogen atoms and up to two further aromatic carbon rings may be fused to the heterocycle and Rl to R5 have the meaning given above.
  • 1- (Benzotriazol-1-yl) -2, -dinitrobenzene can be obtained in 96% yield by boiling benzotriazole with 2,4-dinitrochlorobenzene in toluene for 9 days (A.R. Katritzky, J. Wu, Synthesis 1994, 597).
  • 4-heterocyclically substituted nitrobenzenes and benzaldehydes can be obtained by reacting the respective aza heterocycles, e.g. Benzotriazole, 1, 2, 4-triazole or benzimidazole with 4-fluorobenzaldehyde or 4-fluoro- or 4-chloro-benzaldehyde can be obtained in DMSO or DMF at 100 ° C (DJ Gale, JFK Wilshire, Aust. J. Chem. 23, 1063, 1970; J. Rosevear, JKF Wilshire, Aust. J. Chem. 44, 1097, 1991).
  • Benzotriazole, 1, 2, 4-triazole or benzimidazole with 4-fluorobenzaldehyde or 4-fluoro- or 4-chloro-benzaldehyde can be obtained in DMSO or DMF at 100 ° C (DJ Gale, JFK Wilshire, Aust. J. Chem. 23, 1063, 1970; J. Roseve
  • Nitrophenylazoles can by Ullmann condensation of azoles with aryl halides in pyridine in the presence of potassium carbonate and copper (II) oxide at high temperatures and long reaction times (MA Khan, JB Polya, J. Chem. Soc. (C), 1970, 85; AK Khan , EK Rocha, Chem. Pharm.
  • nucleophiles V to X also react with 2-fluoronitrobenzene at room temperature in the cesium carbonate / dimethylformide system: illustration 1
  • R 1 to R 5 have the meaning given above and HAL stands for a halogen atom, but in particular for a fluorine atom, investigated in the system cesium carbonate / dimethyl formamide.
  • dimethylformamide instead of dimethylformamide, other dipolar aprotic solvents such as e.g. Dimethylacetamide, acetonitrile, dimethyl sulfoxide, acetone or N-methylpyrrolidone can be used, but the reaction times at room temperature are then significantly longer and the yields are often lower.
  • dipolar aprotic solvents such as e.g. Dimethylacetamide, acetonitrile, dimethyl sulfoxide, acetone or N-methylpyrrolidone
  • the suspension is poured onto water, the product is extracted with ethyl acetate and the crude product obtained after evaporation of the organic phase is purified using the methods customary in organic chemistry, for example by crystallization or chromatography.
  • the invention is illustrated and explained by the following exemplary embodiments:
  • Example 9 N-2-cyanophenyldiphenylsulfoximide from 2 fluorobenzonitrile and diphenylsulfoximide at 80 ° C for 8 h / toluene -ethanol 10 + 1 / 74.3% / mp 160 ° C
  • Example 10 N-2-cyanophenyldiphenylsulfoximide from 2 fluorobenzonitrile and diphenylsulfoximide at 80 ° C for 8 h / toluene -ethanol 10 + 1 / 74.3% / mp 160 ° C
  • Example 10 N-2-cyanophenyldiphenylsulfoximide from 2 fluorobenzonitrile and diphenylsulfoximide at 80 ° C for 8 h / toluene -ethanol 10 + 1 / 74.3% / mp 160 ° C
  • Example 10 N-2-cyanophenyldiphenylsulfoximide from 2 fluorobenzon
  • N-4-nitrophenyldiphenylsulfoximide from 4-fluoronitrobenzene and diphenylsulfoximide 64 h / toluene -ethanol 10 + 0.5 / 64.1% / mp 166 ° C
  • Example 16 1 - (4-Ethoxycarbonylphenyl) indole from ethyl 4-fluorobenzoate and indole at 80 ° C
  • Example 36 1- (2-nitrophenyl) indole-2-carboxylic acid ethyl ester from 2-fluoronitrobenzene and indole-2-carboxylic acid ethyl ester 58 h / toluene / 47.9% / mp 90 ° C.
  • Example 37 1- (4-nitrophenyl) indole-2-carboxylic acid ethyl ester from 4-fluoronitrobenzene and indole-2-carboxylic acid ethyl ester at 80 ° C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyrrole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

L'invention concerne un procédé qui permet de produire des N-aryl-aza-hétérocycles de formule générale (I). Le procédé consiste à faire réagir des aza-hétérocycles avec des aryl-halogénures activés en présence de carbonate de césium, sans adjonction d'autres catalyseurs et à température ambiante.
EP00916872A 1999-03-30 2000-02-25 Procede permettant d'aryler des aza-heterocycles avec des composes aromatiques actives en presence de carbonate de cesium Withdrawn EP1165512A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19914610 1999-03-30
DE19914610 1999-03-30
PCT/EP2000/001574 WO2000059883A2 (fr) 1999-03-30 2000-02-25 Procede permettant d'aryler des aza-heterocycles avec des composes aromatiques actives en presence de carbonate de cesium

Publications (1)

Publication Number Publication Date
EP1165512A2 true EP1165512A2 (fr) 2002-01-02

Family

ID=7903080

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00916872A Withdrawn EP1165512A2 (fr) 1999-03-30 2000-02-25 Procede permettant d'aryler des aza-heterocycles avec des composes aromatiques actives en presence de carbonate de cesium

Country Status (8)

Country Link
US (2) US6774242B1 (fr)
EP (1) EP1165512A2 (fr)
JP (1) JP2002541143A (fr)
AU (1) AU3806800A (fr)
BR (1) BR0009432A (fr)
CA (1) CA2360923A1 (fr)
MX (1) MXPA01009596A (fr)
WO (1) WO2000059883A2 (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8029454B2 (en) 2003-11-05 2011-10-04 Baxter International Inc. High convection home hemodialysis/hemofiltration and sorbent system
DE102004010999A1 (de) 2004-03-06 2005-09-22 Wella Ag Kationische Naphthyldiazofarbstoffe sowie diese Farbstoffe enthaltende Mittel zur Färbung von Keratinfasern
EP2172449A3 (fr) * 2005-04-06 2011-06-22 Sicor, Inc. Procédé pour la purification de l' Anastrazole
CN104788355A (zh) * 2015-04-02 2015-07-22 聊城大学 一种含氮杂环苯腈或邻苯二腈化合物的合成方法
WO2018165466A1 (fr) * 2017-03-10 2018-09-13 Regents Of The University Of Minnesota Composés de type indole et indazole et utilisations thérapeutiques correspondantes
CN106866561B (zh) * 2017-04-11 2019-04-23 中国工程物理研究院化工材料研究所 硝基或二硝基苯基-苯并[1,2,3]三唑、衍生物及制备方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5977361A (en) * 1997-10-16 1999-11-02 Yale University Transition metal-catalyzed process for preparing N-aryl compounds

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0059883A2 *

Also Published As

Publication number Publication date
US6774242B1 (en) 2004-08-10
US6933390B2 (en) 2005-08-23
MXPA01009596A (es) 2003-10-14
CA2360923A1 (fr) 2000-10-12
JP2002541143A (ja) 2002-12-03
WO2000059883A2 (fr) 2000-10-12
WO2000059883A3 (fr) 2001-09-13
BR0009432A (pt) 2002-01-08
AU3806800A (en) 2000-10-23
US20040249185A1 (en) 2004-12-09

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