EP0649408A1 - Verfahren zum herstellung von phenylthiomethylpyridinylalkenoaten - Google Patents

Verfahren zum herstellung von phenylthiomethylpyridinylalkenoaten

Info

Publication number
EP0649408A1
EP0649408A1 EP93916841A EP93916841A EP0649408A1 EP 0649408 A1 EP0649408 A1 EP 0649408A1 EP 93916841 A EP93916841 A EP 93916841A EP 93916841 A EP93916841 A EP 93916841A EP 0649408 A1 EP0649408 A1 EP 0649408A1
Authority
EP
European Patent Office
Prior art keywords
formula
phenyl
halo
lower alkoxy
group
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Withdrawn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
EP93916841A
Other languages
English (en)
French (fr)
Other versions
EP0649408A4 (de
Inventor
Robert A. Daines
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.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
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 SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Publication of EP0649408A1 publication Critical patent/EP0649408A1/de
Publication of EP0649408A4 publication Critical patent/EP0649408A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5

Definitions

  • This invention covers a method for making a compound of formula I
  • Formula II Formula II Formula HI where Ri is defined above and (R) n is hydrogen or one or more radicals which can be substituted on either the pyridyl or phenyl ring and m is 0 - 5.
  • the imdefined carbonyl function valence can be a carbon- carbon bond, a carbon-heteroatom bond wherein the heteroatom is oxygen, nitrogen, sulfur or the like, including phosphorus.
  • This invention is intended to cover all the enventualities where a thiol of the type illustrated is reacted with a pyridyl derivative which has an ⁇ , ⁇ -unsaturated carbonyl system at the 2-position which can undergo a Michael addition reaction with the thiol.
  • a given group may be in protected form, for example a carboxylate function may be present in the form of an ester, the acid being regenerated by hydrolytic, catalytic or enzymatic means once the coupling reaction is completed.
  • the invention is that of the use of DBU to affect the coupling of the chloro and the thiol to achieve the thioether and is to be viewed as only so limited.
  • aliphatic is intended to include saturated and unsaturated radicals. This includes normal and branched chains, saturated or mono or poly unsaturated chains where both double and triple bonds may be present in any combination.
  • lower alkyl means an alkyl group of 1 to 6 carbon atoms in any isomeric form, but particularly the normal or linear form.
  • Lower alkoxy means the group lower alkyl-O-.
  • Acyl-lower alkyl refers to the group (O)C-lower alkyl where the carbonyl carbon is counted as one of the carbons of the 1 to 6 carbons noted under the definition of lower alkyl.
  • Halo refers to and means fluoro, chloro, bromo or iodo. The phenyl ring may be substituted with one or more of these radicals.
  • substituents may be the same or different, such as where there are three chloro groups, or a combination of chloro and alkyl groups and further where this latter combination may have different alkyl radicals in the chloro/alkyl pattern.
  • Oxides of the pyridyl ring nitrogen may be prepared by means known in the art and as illustrated herein. These are to be considered part of the invention.
  • Cio-alip atic where substituted phenyl has one or more radicals selected from the group consisting of lower alkoxy, lower alkyl, trihalomethyl, and halo, or R is Cj to C20-aliphatic-O-, or R is unsubstituted or substituted phenyl-Ci to CiQ-al ⁇ hatic-O- where substituted phenyl has one or more radicals selected from the group consisting of lower alkoxy, lower alkyl, trihalomethyl, and halo;
  • R2 is H, lower alkoxy, halo, -CN, -(CH2) n R4 where n is 0 - 5, lower alkyl, or CF3;
  • R4 is tetrazol-5-yl or COR5; and R5 is lower alkoxy, C ⁇ O- ⁇ 0 or phenyl(CH2) ⁇ -3CO.
  • Trmlring the right hand portion of formula I can be purchased from o commercial sources.
  • a fist is as follows: 2,5-dichlorothiophenol, 2,6-dimethylthiophenol,2-chloro-6-fluorobenzyl mercaptan, and 2,4-difluorobenzyl thiol.
  • Other thiols can be made by published chemistry; that chemistry involves converting a haloalkylphenyl (the bromo form is preferred) compound to the corresponding mercaptan by treating the bromo compound with thiourea followed by base hydrolysis.
  • the thiophenols can be prepared by thermal rearrangement of the corresponding thiocarbamate followed by hydrolysis.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
EP93916841A 1992-06-30 1993-06-30 Verfahren zum herstellung von phenylthiomethylpyridinylalkenoaten. Withdrawn EP0649408A4 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US906951 1986-09-15
US90695192A 1992-06-30 1992-06-30
US2520093A 1993-03-02 1993-03-02
US25200 1993-03-02
PCT/US1993/006177 WO1994000433A1 (en) 1992-06-30 1993-06-30 Process for making phenylthiomethylpyridinylalkenoates

Publications (2)

Publication Number Publication Date
EP0649408A1 true EP0649408A1 (de) 1995-04-26
EP0649408A4 EP0649408A4 (de) 1995-06-21

Family

ID=26699426

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93916841A Withdrawn EP0649408A4 (de) 1992-06-30 1993-06-30 Verfahren zum herstellung von phenylthiomethylpyridinylalkenoaten.

Country Status (10)

Country Link
EP (1) EP0649408A4 (de)
JP (1) JP3181917B2 (de)
KR (1) KR950702184A (de)
CN (1) CN1095713A (de)
AU (1) AU678979B2 (de)
CA (1) CA2138955A1 (de)
MX (1) MX9303972A (de)
NZ (1) NZ254473A (de)
TW (1) TW247907B (de)
WO (1) WO1994000433A1 (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0733044A4 (de) * 1993-12-08 1997-03-05 Smithkline Beecham Corp Chemische verbindungen
GB9508137D0 (en) * 1995-04-21 1995-06-07 Smithkline Beecham Plc Formulation
CN1314666C (zh) * 2005-12-19 2007-05-09 华中师范大学 微波辅助合成硫醚类化合物的方法
KR200481393Y1 (ko) * 2014-08-06 2016-09-27 김상열 스마트 슬림 스탠드

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991018601A1 (en) * 1990-06-07 1991-12-12 Smithkline Beecham Corporation Benzoic acid derivatives

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3810379A1 (de) * 1988-03-26 1989-10-12 Hoechst Ag Azaneophyl- und silazaneophylsulfide, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als schaedlingsbekaempfungsmittel
EP0548291A1 (de) * 1990-09-13 1993-06-30 Smithkline Beecham Corporation Pyridylthio- und pyridyloxy-alkancarbonsäurederivate
WO1993006085A1 (en) * 1991-09-19 1993-04-01 Smithkline Beecham Corporation Pyridine compounds for treating leukotriene-related diseases

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991018601A1 (en) * 1990-06-07 1991-12-12 Smithkline Beecham Corporation Benzoic acid derivatives

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO9400433A1 *

Also Published As

Publication number Publication date
WO1994000433A1 (en) 1994-01-06
CA2138955A1 (en) 1994-01-06
TW247907B (de) 1995-05-21
KR950702184A (ko) 1995-06-19
AU4655793A (en) 1994-01-24
MX9303972A (es) 1994-04-29
JPH07508283A (ja) 1995-09-14
JP3181917B2 (ja) 2001-07-03
CN1095713A (zh) 1994-11-30
AU678979B2 (en) 1997-06-19
NZ254473A (en) 1996-11-26
EP0649408A4 (de) 1995-06-21

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