EP0885195A1 - Process for the preparation of substituted pyridine derivatives - Google Patents

Process for the preparation of substituted pyridine derivatives

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Publication number
EP0885195A1
EP0885195A1 EP97904364A EP97904364A EP0885195A1 EP 0885195 A1 EP0885195 A1 EP 0885195A1 EP 97904364 A EP97904364 A EP 97904364A EP 97904364 A EP97904364 A EP 97904364A EP 0885195 A1 EP0885195 A1 EP 0885195A1
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EP
European Patent Office
Prior art keywords
formula
hydrogen
compound
process according
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.)
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Application number
EP97904364A
Other languages
German (de)
French (fr)
Inventor
Richard Keith SmithKline Beecham Pharm. ANDERSON
Peter Willaim SmithKline Beecham Pharm SHELDRAKE
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SmithKline Beecham Ltd
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SmithKline Beecham Ltd
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Publication of EP0885195A1 publication Critical patent/EP0885195A1/en
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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
    • C07D213/60—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

  • PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIDINE DERIVATIVES PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIDINE DERIVATIVES .
  • the present invention relates to a novel process for the preparation of substituted pyridine derivatives.
  • Substituted pyridine derivatives are disclosed in WO93/06085 as medicaments being useful for the treatment of various diseases such as psoriasis.
  • WO95/00487 discloses a process for the preparation of pyridine derivatives by palladium catalysed vinylic substitution reactions.
  • the object of the present invention is to provide an alternative process to that disclosed in WO95/00487 using organometallic coupling chemistry carried out on a thioether precursor.
  • a particular advantage of the present invention is that formation of compounds having an undesired cis-olefin is avoided. Furthermore, it is surprising that the organometallic coupling proceeds efficiently in the presence of a thioether compound since divalent sulphur is generally known to be a catalyst poison.
  • the present invention therefore provides a process for the preparation of a compound of formula (I) or a salt thereof:
  • Rl is hydrogen, benzyl or a group of formula (A):
  • n 1 to 20 and R ⁇ is hydrogen, Cj.galkyl, C ⁇ _6alkoxy or trifluoromethyl; m is O to 5; R8 and R ⁇ are independently hydrogen, halogen, CO2H, C j .galkyl or
  • Suitable organometallic catalysts include, for example, palladium catalysts.
  • palladium catalysts can, if desired, be formed in situ. The processes of the invention can be carried out using pre-prepared catalysts or catalysts formed in situ.
  • Preferred catalysts are palladium (II) catalysts such as Pd(OAc)2, Pd(OAc)2/(o-tol)3P, Pd(OAc)2/Ph3P, Pd(OAc)2/tri(2-furyl)phosphine, (Ph3P)2PdCl2 and Most preferably the catalyst is Pd(OAc)2/ Ph3P.
  • R is a group of formula (A) where R* is hydrogen.
  • n is 1 to 20, preferably n is 2 to 8, most preferably n is 2.
  • m is 0 to 5, preferably m is 0.
  • R 2 and R 3 are hydrogen or Cj.galkyl, preferably R 2 and R 3 are both hydrogen.
  • R 4 is suitably cyano or CO2R where R ⁇ is hydrogen or Cj. ⁇ alkyl.
  • R 4 is CO2 6 where R > is Cj. ⁇ alkyl such as methyl, ethyl or butyl.
  • R? is a leaving group such as halogen, OTf or OSO2Ar where Ar is an optionally substituted aryl group. Suitable substituents for Ar groups include C ⁇ _6alkyl, for example methyl. Preferably R? is halogen, in particular bromo or iodo.
  • Compounds of formula (I) can be converted into further compounds of formula (I) using standard procedures.
  • a compound of formula (I) in which R' is benzyl may be converted into a compound of formula (I) in which R' is hydrogen by hydrogenation.
  • Compounds of formula (I) in which R 4 is CO2 where R*> is Cj_6alkyl can be converted into compounds of formula (I) in which R 4 is CO2H using standard ester hydrolysis procedures.
  • Preferred compounds of formula (I) which can be prepared using the above processes include:
  • the organometallic coupling reaction is carried out in a suitable solvent or mixture of solvents, preferably at elevated temperature.
  • the coupling reaction is carried out in dimethylacetamide or DMF, in particular aqueous dimethylacetamide or DMF, at a temperature of about 80 to about 160°C, preferably at about 140°C.
  • the amount of water present is suitably about 0.2 to about 15%, preferably about 0.2 to about 10% and more preferably about 5%.
  • Diol solvents such as propane- 1,2-diol can also be used.
  • salts of compounds of formula (III) refers to carboxylate salts of compounds of formula (III), in which R 4 is CO2 M® where M is a metal ion such as sodium or potassium. Examples of such compounds include sodium and potassium acrylate. Salts of compounds of formula (I) can be prepared by treatment with an inorganic or organic acid, or when R 4 is CO2H, by treatment with an inorganic or organic base.
  • compounds of formula (II) in which Rl is benzyl or a group of formula (A) can be prepared by reaction of a compound of formula (IV):
  • R ⁇ is benzyl or a group of formula (A) and R' is as defined in formula (II) and X is a leaving group with a compound of formula (V):
  • Suitably leaving groups X include, for example, halo, C]_6 lkylSO2 such as methanesulphonyl or ArSO2 where Ar is optionally substituted phenyl, for example p- toluenesulphonyl.
  • X is halo in particular chloro.
  • Compounds of formula (IV) where X is halo can be prepared in situ from the corresponding compound where X is hydroxy, for example by treatment with thionyl chloride.
  • a salt of a compound (I) should be pharmaceutically acceptable.
  • pharmaceutically acceptable salts include inorganic and organic acid addition salts such as hydrochloride, hydrobromide, sulphate, phosphate, acetate, fumarate, maleate, citrate, lactate, tartrate, oxalate, methanesulphonate or similar pharmaceutically acceptable inorganic or organic acid addition salts.
  • preferred salts include the sodium and potassium salts.
  • salts may be used for example in the isolation of intermediate or final products and are included within the scope of this invention.
  • R 4 is CO2H
  • salts can be prepared by treatment with an inorganic or organic base.
  • the invention provides a compound of formula (I) whenever prepared by a process as described above, and in particular [[1 -thia-2-[6-(E-2-carboxyethenyl)5- phenylethyloxy-2-pyridyl]]ethyl]-2,6-dichlorobenzene and salts thereof whenever prepared by the above processes.
  • IR (nujol mull) 1600, 1552, 1500, 1425, 1300, 1275, 1075, 1015, 828, 775, 750, 740, 700 cm"'.
  • the aqueous phase was adjusted to pH 4.1 using concentrated hydrochloric acid and the mixture was filtered through Celite. The layers were separated and the aqueous layer was extracted with ethyl acetate (25 ml). The combined organic layers were washed with water (3 x 20 ml) and distilled at atmospheric pressure to a volume of 45 ml. The solution was diluted with hexane (45 ml), seeded and cooled in an ice/water bath for 1 hour. The solid was filtered off, washed with 1 : 1 ethyl acetate :hexane (10 ml) and dried under vacuum at ambient temperature overnight to give the title compound (3.4g 74%), Mpt. 143 - 5°C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

The invention relates to a novel process for the preparation of substituted pyridine derivatives of formula (I) or a salt thereof, in which: R1 is hydrogen, benzyl or a group of formula (A): where n is 1 to 20 and R5 is hydrogen, C¿1-6?alkyl, C1-6alkoxy or trifluoromethyl; m is 0 to 5; R?8 and R9¿ are independently hydrogen, halogen, CO¿2?H, C1-6alkyl or C1-6alkoxy; and R?10¿ is a group CR?2=CR3-R4 or CHR2-CHR3-R4¿ where R?2 and R3¿ are independently hydrogen or C¿1-6?alkyl and R?4¿ is cyano or CO¿2R?6 is hydrogen or C¿1-6?alkyl, and starting from a compound of formula (II), in which m, R?1, R8 and R9¿ are as defined in formula (I) and R7 is a leaving group by palladium catalysed vinylic substitution reactions.

Description

PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIDINE DERIVATIVES .
The present invention relates to a novel process for the preparation of substituted pyridine derivatives. Substituted pyridine derivatives are disclosed in WO93/06085 as medicaments being useful for the treatment of various diseases such as psoriasis.
Various processes for the preparation of these medicaments are also disclosed in WO93/06085 and WO95/00487. In particular, WO95/00487 discloses a process for the preparation of pyridine derivatives by palladium catalysed vinylic substitution reactions.
The object of the present invention is to provide an alternative process to that disclosed in WO95/00487 using organometallic coupling chemistry carried out on a thioether precursor. A particular advantage of the present invention is that formation of compounds having an undesired cis-olefin is avoided. Furthermore, it is surprising that the organometallic coupling proceeds efficiently in the presence of a thioether compound since divalent sulphur is generally known to be a catalyst poison.
In a first aspect the present invention therefore provides a process for the preparation of a compound of formula (I) or a salt thereof:
(I)
in which:
Rl is hydrogen, benzyl or a group of formula (A):
(A)
where n is 1 to 20 and R^ is hydrogen, Cj.galkyl, Cι _6alkoxy or trifluoromethyl; m is O to 5; R8 and R^ are independently hydrogen, halogen, CO2H, Cj.galkyl or
Cj.galkoxy; and
R10 is a group CR2=CR3-R4 or CHR2-CHR3-R4 where R2 and R3 are independently hydrogen or C]_6alkyl and R4 is cyano or CO2R6 where R^ is hydrogen or Cj.galkyl, which process comprises: coupling a compound of formula (II):
(II)
in which m, R^ , R^ and R^ are as defined in formula (I) and R? is a leaving group with a compound of formula (III) or a salt thereof:
3 R
2 R
(III) in which R2, R3 and R4 are as defined in formula (I) in the presence of an organometallic catalyst, and optionally thereafter: • converting a compound of formula (I) into another compound of formula (I) • forming a pharmaceutically acceptable salt.
Suitable organometallic catalysts include, for example, palladium catalysts. Those skilled in the art will appreciate that palladium catalysts can, if desired, be formed in situ. The processes of the invention can be carried out using pre-prepared catalysts or catalysts formed in situ. Preferred catalysts are palladium (II) catalysts such as Pd(OAc)2, Pd(OAc)2/(o-tol)3P, Pd(OAc)2/Ph3P, Pd(OAc)2/tri(2-furyl)phosphine, (Ph3P)2PdCl2 and Most preferably the catalyst is Pd(OAc)2/ Ph3P.
Preferably R is a group of formula (A) where R* is hydrogen.
Suitably n is 1 to 20, preferably n is 2 to 8, most preferably n is 2. Suitably m is 0 to 5, preferably m is 0.
Suitably R2 and R3 are hydrogen or Cj.galkyl, preferably R2 and R3 are both hydrogen.
In compounds of formula (III) R4 is suitably cyano or CO2R where R^ is hydrogen or Cj.^alkyl. Preferably R4 is CO2 6 where R > is Cj.^alkyl such as methyl, ethyl or butyl.
Suitably R? is a leaving group such as halogen, OTf or OSO2Ar where Ar is an optionally substituted aryl group. Suitable substituents for Ar groups include Cι_6alkyl, for example methyl. Preferably R? is halogen, in particular bromo or iodo.
Compounds of formula (I) can be converted into further compounds of formula (I) using standard procedures. For example a compound of formula (I) in which R' is benzyl may be converted into a compound of formula (I) in which R' is hydrogen by hydrogenation. Compounds of formula (I) in which R4 is CO2 where R*> is Cj_6alkyl can be converted into compounds of formula (I) in which R4 is CO2H using standard ester hydrolysis procedures. Compounds of formula (I) in which the dotted line represents a double bond, that is to say forming a group CR =CR -R4, can be converted to the corresponding saturated compounds having the group CHR -CHR -R4 by hydrogenation.
Preferred compounds of formula (I) which can be prepared using the above processes include:
[[l-thia-2-[6-(E-2-carboxyethenyl)5-phenylethyloxy-2-pyridyl]]ethyl]-2,6-dichlorobenzene and salts thereof.
The organometallic coupling reaction is carried out in a suitable solvent or mixture of solvents, preferably at elevated temperature. Preferably the coupling reaction is carried out in dimethylacetamide or DMF, in particular aqueous dimethylacetamide or DMF, at a temperature of about 80 to about 160°C, preferably at about 140°C. The amount of water present is suitably about 0.2 to about 15%, preferably about 0.2 to about 10% and more preferably about 5%. Diol solvents such as propane- 1,2-diol can also be used.
The term 'salts' in relation to compounds of formula (III) refers to carboxylate salts of compounds of formula (III), in which R4 is CO2 M® where M is a metal ion such as sodium or potassium. Examples of such compounds include sodium and potassium acrylate. Salts of compounds of formula (I) can be prepared by treatment with an inorganic or organic acid, or when R4 is CO2H, by treatment with an inorganic or organic base.
Compounds of formulae (II) and (III) are commercially available or can be prepared using standard procedures well known to those skilled in the art.
For example, compounds of formula (II) in which Rl is benzyl or a group of formula (A) can be prepared by reaction of a compound of formula (IV):
OR1
R'
(IV)
in which R^ is benzyl or a group of formula (A) and R' is as defined in formula (II) and X is a leaving group with a compound of formula (V):
(V)
in which m, R^ and R^ are as defined in formula (I).
Suitably leaving groups X include, for example, halo, C]_6 lkylSO2 such as methanesulphonyl or ArSO2 where Ar is optionally substituted phenyl, for example p- toluenesulphonyl. Preferably X is halo in particular chloro. Compounds of formula (IV) where X is halo can be prepared in situ from the corresponding compound where X is hydroxy, for example by treatment with thionyl chloride.
It will be appreciated that for use in medicine a salt of a compound (I) should be pharmaceutically acceptable. Examples of pharmaceutically acceptable salts include inorganic and organic acid addition salts such as hydrochloride, hydrobromide, sulphate, phosphate, acetate, fumarate, maleate, citrate, lactate, tartrate, oxalate, methanesulphonate or similar pharmaceutically acceptable inorganic or organic acid addition salts.
4 When R is CO2H preferred salts include the sodium and potassium salts.
Other non-pharmaceutically acceptable salts may be used for example in the isolation of intermediate or final products and are included within the scope of this invention. When R4 is CO2H, salts can be prepared by treatment with an inorganic or organic base.
In a further aspect the invention provides a compound of formula (I) whenever prepared by a process as described above, and in particular [[1 -thia-2-[6-(E-2-carboxyethenyl)5- phenylethyloxy-2-pyridyl]]ethyl]-2,6-dichlorobenzene and salts thereof whenever prepared by the above processes.
The following examples illustrate the invention.
Example 1 l-Bromo-5-[(2,6-dichlorophenyl)thiomethyl]-2-(2-phenethyloxy)pyridine
2-Bromo-6-hydroxymethyl-3-(2-phenylethyl)oxypyridine SB-221787 (5.0 g, 16.2 mmole) was dissolved in dichloromethane (50 ml) and DMF (1 drop) was added. Thionyl chloride (2.34 ml, 3.81 g, 32 mmole) was addded and the solution was stirred at ambient temperature for 30 minutes. The solution was evaporated to dryness, the residue was dissolved in toluene (50 ml) and this solution was evaporated to dryness. The residue was dissolved in ethanol (30 ml).
Potassium hydroxide (2.29 g, 34.7 mmole) was dissolved in ethanol (50 ml). To the solution was added 2,6-dichlorothiophenol (2.90 g, 16.2 mmole) and the mixture was stirred until all the solid dissolved. To this solution was added the above solution of the chloromethylpyridine. The reaction was stirred at ambient temperature for 2 hours. Most of the ethanol was evaporated and water (60 ml) and dichloromethane (60 ml) were added. The layers were shaken and separated. The aqueous layer was again extracted with dichloromethane. The combined organic layers were washed with 10% sodium bicarbonate solution and with water; then dried (sodium sulfate) and evaporated to to leave a solid (6.74 g). This solid was recrystallised from ethanol to give the title compound (5.91 g, 78%) which was dried under vacuum at ambient temperature. M.p. 70 - 80 °C.
IR (nujol mull) 1600, 1552, 1500, 1425, 1300, 1275, 1075, 1015, 828, 775, 750, 740, 700 cm"'.
Nmr (CDCI3) δ (ppm): 3.15 (2H, t, J = 7Hz), 4.10 (2H, s), 4.15 (2H, t, J = 7Hz), 6.90 (IH, d, J = 7Hz), 6.98 (IH, d, J = 7Hz), 7.14 (IH, dd, J = 7Hz, 8Hz), 7.20 - 7.40 (7H).
Example 2
(E)-Ethyl 3-[-[[2,6-dichlorophenyl)thiomethyl]-3-(2-phenethyloxy-2-pyridinyl]-2- propenoate hydrochloride
l-Bromo-5-[(2,6-dichlorophenyl)thiomethyl]-2-(2-phenethyloxy)pyridine (4.70g, 10.0 mmole), tetra-n-butylammonium iodide (3.69g, 10.0 mmole) and potassium acetate (2.45g, 10.0 mmole) were charged to a flask and dissolved in dimethylacetamide (17 ml) and water (0.4 ml). To the solution was added palladium acetate (0.09 g, 0.4 mmole), triphenylphosphine (0.21 g, 0.8 mmole) and ethyl acrylate (3.25 ml, 3.00 g, 30 mmole). The mixture was placed under nitrogen and stirred and heated to 140° for 1 hour. The reaction was cooled and water (25 ml) and ethyl acetate (25 ml) were added. The layers were shaken and separated. The aqueous phase was again extracted with ethyl acetate (2 x 12 ml). The combined organic layers were washed with water (3 x 15 ml) and fitered through Celite. The filtrate was evaporated to a brown syrup (6.05g). This was purified by flash chromatography on silica eluting with toluene, then 5% ethyl acetate in toluene to give the title compound (3.90 g 80%) as an oil.
IR (f-Im) 1722, 1640, 1572, 1552, 1455, 1425, 1310, 1270 (br), 1170 (br), 1 110, 1030,
990, 880, 830, 780, 750, 700 cm"1.
Nmr (CDC13) δ (ppm): 1.36 (3H, t, J = 7Hz), 3.14 (2H, t, J = 6Hz), 4.12 (2H, s), 4.17 (2H, t, J = 6Hz), 4.25 (2H, q, J = 7Hz), 6.64 (IH, d, J = 15Hz), 7.00 - 7.20 (3H), 7.20 - 7.40
(7H), 7.94 (1 H, d J = 15Hz).
Example 3
[ 11 -thia-2- [6-(E-2-carboxyethenyl)5-phenylethyIoxy-2-pyridyl] ] ethyl] -2,6- dichlorobenzene
In a reaction vessel protected from light, the foregoing ester (E)-ethyl 3-[-[[2,6- dichlorophenyl)thiomethyl]-3-(2-phenethyloxy-2-pyridinyl]-2-propenoate (5.05 g, 10 mmole) was dissolved in ethanol (30 ml) and 5M aqueous sodium hydroxide solution (3.0 ml 15 mmole) was added. The reaction was heated at reflux for 30 minutes. The solution was cooled and most of the ethanol was evaporated. Ethyl acetate (50 ml) and water (50 ml) were added to the residue. The aqueous phase was adjusted to pH 4.1 using concentrated hydrochloric acid and the mixture was filtered through Celite. The layers were separated and the aqueous layer was extracted with ethyl acetate (25 ml).The combined organic layers were washed with water (3 x 20 ml) and distilled at atmospheric pressure to a volume of 45 ml. The solution was diluted with hexane (45 ml), seeded and cooled in an ice/water bath for 1 hour.The solid was filtered off, washed with 1 : 1 ethyl acetate :hexane (10 ml) and dried under vacuum at ambient temperature overnight to give the title compound (3.4g 74%), Mpt. 143 - 5°C. IR 1686, 1633, 1571, 1552, 1263, 1110, 777, 752, 697 cm-1. Nmr (CDCI3) δ (ppm): 3.14 (2H, t, J = 7Hz), 4.15 (2H, s), 4.19 (2H, t, J = 7Hz), 6.63 (IH, d, J = 16Hz), 7.08 (IH, d, J = 8.5Hz), 7.16 (IH, m), 7.18 (IH, d, J = 8.5Hz), 7.22 - 7.38 (7H), 8.03 (lH, d, J = 16Hz).

Claims

Claims:
A process for the preparation of a compound of formula (I) or a salt thereof:
(I)
in which: R' is hydrogen, benzyl or a group of formula (A):
(A)
where n is 1 to 20 and R^ is hydrogen, Cj.galkyl, Ci.galkoxy or trifluoromethyl; m is 0 to 5;
R8 and R9 are independently hydrogen, halogen, CO2H, Ci .galkyl or
Ci .galkoxy; and
R10 is a group CR2=CR3-R4 or CHR2-CHR3-R4 where R2 and R3 are independently hydrogen or C \ _6alkyl and R4 is cyano or CO2R where R^ is hydrogen or C 1.βalkyl, which process comprises: coupling a compound of formula (II):
(H)
in which m, R , R8 and R9 are as defined in formula (I) and R7 is a leaving group with a compound of formula (III) or a salt thereof: 3
R
I 2
R
(III) in which R2, R3 and R4 are as defined in formula (I) in the presence of an organometallic catalyst, and optionally thereafter:
• converting a compound of formula (I) into another compound of formula (I)
• forming a pharmaceutically acceptable salt.
2. A process according to claim 1 in which the catalyst is a palladium derivative.
3. A process according to claim 2 in which the catalyst is Pd(OAc)2/ Ph3P.
4. A process according to any one of claims 1 to 3 in which the palladium coupling is carried out in aqueous dimethylacetamide or DMF.
5. A process according to any one of claims 1 to 4 in which R' is a group of formula (A) where n is 2 to 8.
6. A process according to any one of claims 1 to 5 in which R4 is CO2R where R6 is hydrogen or Cι_6alkyl.
7. A process according to any one of claims 1 to 7 in which R^ is hydrogen.
8. A process according to claim 1 in which the compound prepared is:
[[l-thia-2-[6-(E-2-carboxyethenyl)5-phenylethyloxy-2-pyridyl]]ethyl]-2,6-dichlorobenzene or a salt thereof.
9. [[l-thia-2-[6-(E-2-carboxyethenyl)5-phenylethyloxy-2-pyridyl]]ethyl]-2,6- dichlorobenzene or a salt thereof whenever prepared using a process according to any one of claims 1 to 7.
EP97904364A 1996-02-09 1997-01-27 Process for the preparation of substituted pyridine derivatives Withdrawn EP0885195A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9602675.2A GB9602675D0 (en) 1996-02-09 1996-02-09 Process
GB9602675 1996-02-09
PCT/EP1997/000447 WO1997029089A1 (en) 1996-02-09 1997-01-27 Process for the preparation of substituted pyridine derivatives

Publications (1)

Publication Number Publication Date
EP0885195A1 true EP0885195A1 (en) 1998-12-23

Family

ID=10788432

Family Applications (1)

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Country Status (4)

Country Link
EP (1) EP0885195A1 (en)
JP (1) JP2000505427A (en)
GB (1) GB9602675D0 (en)
WO (1) WO1997029089A1 (en)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MA22926A1 (en) * 1992-06-30 1994-04-01 Smithkline Beecham Corp PROCESS FOR THE PREPARATION OF NEW COMPOUNDS.
GB9313145D0 (en) * 1993-06-25 1993-08-11 Smithkline Beecham Plc Process
GB9508137D0 (en) * 1995-04-21 1995-06-07 Smithkline Beecham Plc Formulation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9729089A1 *

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WO1997029089A1 (en) 1997-08-14
GB9602675D0 (en) 1996-04-10
JP2000505427A (en) 2000-05-09

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