EP0000301B1 - Verfahren zur Herstellung von Thieno(2,3-c) und Thieno(3,2-c) Pyridinen - Google Patents

Verfahren zur Herstellung von Thieno(2,3-c) und Thieno(3,2-c) Pyridinen Download PDF

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Publication number
EP0000301B1
EP0000301B1 EP78400018A EP78400018A EP0000301B1 EP 0000301 B1 EP0000301 B1 EP 0000301B1 EP 78400018 A EP78400018 A EP 78400018A EP 78400018 A EP78400018 A EP 78400018A EP 0000301 B1 EP0000301 B1 EP 0000301B1
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EP
European Patent Office
Prior art keywords
acid
formula
thieno
derivatives
carboxy
Prior art date
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Expired
Application number
EP78400018A
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English (en)
French (fr)
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EP0000301A1 (de
Inventor
Jean-Pierre Maffrand
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Sanofi SA
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Sanofi SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to a new process for the preparation of thieno [2,3-c] and thieno [3,2-c] pyridines of formulas: in which R represents hydrogen or the carboxy group.
  • R represents hydrogen or the carboxy group.
  • the object of the present invention is to provide an inexpensive synthesis process making it possible to obtain, with good yields, the compounds (I) and (II) which are important intermediates in the chemical and pharmaceutical industry, in particular for the preparation of thienopyridine derivatives having various therapeutic activities, for example anti-inflammatory, anti-platelet aggregation, anti-arrhythmic, etc. (see for example the patents and published French patent applications No. 2 215 948, 2 257,271, 2,315,274 and 2,345,150.
  • the process of the invention is characterized in that a compound of formula is reacted with nitrous acid, thus obtaining compounds of formula and reacting the compounds of formula (V) or (VI) respectively with an acid, thereby obtaining the derivatives of formula (I) and (II) respectively in which R is hydrogen, or with an alkali metal hydroxide and subsequent neutralization, thereby obtaining the derivatives of formula (I) and (II) respectively in which R is the carboxy group.
  • nitrous acid is formed in situ by reacting an alkali metal nitrite in aqueous solution with an acid.
  • the reaction is carried out in particular by slowly adding an aqueous solution of alkali metal nitrite, in particular sodium, to a hydrochloric solution, maintained at 0 ° -15 ° C., of the derivative of formula (III) or (IV) then leaving for several hours at room temperature.
  • alkali metal nitrite in particular sodium
  • a mineral acid such as hydrochloric acid, hydrobromic acid or sulfuric acid, preferably hydrochloric acid
  • an organic acid such as trifluoroacetic acid or trichloroacetic acid, preferably trifluoroacetic acid
  • the starting compounds of formula (III) or (IV) can be prepared by reaction of a compound of formula with formaldehyde in aqueous solution, in the presence of a strong acid.
  • Example 3 By operating as in Example 3, starting from the nitrose compound obtained in Example 1, thieno [2,3-c] pyridine is obtained. F ⁇ 50 ° C, yield: 47%.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Claims (9)

1. Verfahren zur Herstellung von Thieno[2,3-c]- und Thieno[3,2-c]pyridinderivaten der allgemeinen Formel
Figure imgb0012
worin R Wasserstoff oder Carboxyl bedeutet, dadurch gekennzeichnet, dass man eine Verbindung der Formel
Figure imgb0013
mit salpetriger Säure umsetzt und die so erhaltenen Verbindungen der Formel
Figure imgb0014
entweder mit einer Säure, wobei die Verbindungen (I) bzw. (11), worin R Wasserstoff bedeutet, erhalten werden, oder mit einem Alkalimetallhydroxyd und anschliessende Neutralisation, wobei die Verbindungen (i) bzw. (11), worin R Carboxyl bedeutet, erhalten werden, umsetzt.
2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man die salpetrige Säure in situ durch Umsetzen eines Alkalimetallnitrits in wässeriger Lösung mit einer Säure bildet.
3. Verfahren nach Anspruch 2, dadurch gekennzeichnet, dass man als Säure Salzsäure einsetzt.
4. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man die Entfernung der Nitrosogruppe mittels einer Säure mit einer Mineralsäure oder einer organischen Säure bewirkt.
5. Verfahren nach Anspruch 4, dadurch gekennzeichnet, dass man als Mineralsäure Salzsäure einsetzt.
6. Verfahren nach Anspruch 4, dadurch gekennzeichnet, dass man als organische Säure Trifluoressigsäure einsetzt.
7. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man die Entfernung der Nitrosogruppe mittels eines Alkalimetallhydroxyds in wässeriger Lösung bei Rückflusstemperatur bewirkt.
8. Verfahren nach Anspruch 1, dadurch gekennzeichnet, dass man eine Verbindung der Formel (I) oder (II), worin R Carboxyl bedeutet, zu einer Verbindung (I) oder (11), worin R Wasserstoff ist, decarboxyliert.
9. Verfahren nach Anspruch 8, dadurch gekennzeichnet, dass man die Decarboxylierung mit Hilfe von Kupferpulver in Anwesenheit von Chinolin durchführt.
EP78400018A 1977-06-21 1978-06-13 Verfahren zur Herstellung von Thieno(2,3-c) und Thieno(3,2-c) Pyridinen Expired EP0000301B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR7718991 1977-06-21
FR7718991A FR2395271A1 (fr) 1977-06-21 1977-06-21 Procede de preparation de thieno (2,3-c) et thieno (3,2-c) pyridines

Publications (2)

Publication Number Publication Date
EP0000301A1 EP0000301A1 (de) 1979-01-10
EP0000301B1 true EP0000301B1 (de) 1980-09-17

Family

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Family Applications (1)

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EP78400018A Expired EP0000301B1 (de) 1977-06-21 1978-06-13 Verfahren zur Herstellung von Thieno(2,3-c) und Thieno(3,2-c) Pyridinen

Country Status (31)

Country Link
US (1) US4161599A (de)
EP (1) EP0000301B1 (de)
JP (1) JPS549298A (de)
AR (1) AR216515A1 (de)
AT (1) AT362372B (de)
AU (1) AU515505B2 (de)
BE (1) BE868272A (de)
CA (1) CA1074800A (de)
CH (1) CH635588A5 (de)
DD (1) DD135492A5 (de)
DE (1) DE2860164D1 (de)
DK (1) DK147827C (de)
ES (1) ES469703A1 (de)
FI (1) FI63236C (de)
FR (1) FR2395271A1 (de)
GB (1) GB1584143A (de)
GR (1) GR64843B (de)
HU (1) HU178316B (de)
IE (1) IE47055B1 (de)
IL (1) IL54780A (de)
IT (1) IT1105427B (de)
LU (1) LU79787A1 (de)
MX (1) MX5020E (de)
NO (1) NO149315C (de)
NZ (1) NZ187625A (de)
PH (1) PH17024A (de)
PL (1) PL113510B1 (de)
PT (1) PT68182A (de)
SU (1) SU728717A3 (de)
YU (1) YU40709B (de)
ZA (1) ZA783051B (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA743814B (en) * 1973-06-15 1976-01-28 Merck & Co Inc Mercaptoalkylpyridines and derivatives
JPS6171830A (ja) * 1984-09-17 1986-04-12 Dainippon Ink & Chem Inc 界面活性剤組成物
US5962490A (en) * 1987-09-25 1999-10-05 Texas Biotechnology Corporation Thienyl-, furyl- and pyrrolyl-sulfonamides and derivatives thereof that modulate the activity of endothelin
DK0746320T3 (da) * 1994-02-02 2001-02-19 Lilly Co Eli HIV-proteaseinhibitorer og mellemprodukter
US5958905A (en) 1996-03-26 1999-09-28 Texas Biotechnology Corporation Phosphoramidates, phosphinic amides and related compounds and the use thereof to modulate the activity of endothelin
US5804585A (en) * 1996-04-15 1998-09-08 Texas Biotechnology Corporation Thieno-pyridine sulfonamides derivatives thereof and related compounds that modulate the activity of endothelin
FR2797874B1 (fr) * 1999-08-27 2002-03-29 Adir Nouveaux derives de la pyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2345150A2 (fr) * 1975-08-06 1977-10-21 Centre Etd Ind Pharma Nouveaux derives de la thienopyridine, et leur application
US3997545A (en) * 1973-07-23 1976-12-14 Takeda Chemical Industries, Ltd. Thienopyridine-carboxylic acid derivatives
FR2263745B1 (de) * 1974-03-12 1977-12-02 Roussel Uclaf
FR2278683A1 (fr) * 1974-07-16 1976-02-13 Parcor Procede de preparation de la thieno(3,2-c)pyridine et de la thieno(2,3-c)pyridine
FR2312498A1 (fr) * 1975-05-30 1976-12-24 Parcor Procede de preparation de la thieno (3,2-c) pyridine et de derives de celle-ci
FR2312247A1 (fr) * 1975-05-30 1976-12-24 Parcor Derives de la thieno-pyridine, leur procede de preparation et leurs applications
FR2315274A1 (fr) * 1975-06-27 1977-01-21 Parcor Nouveaux derives de la thieno (2,3-c) pyridine, leur preparation et leurs applications

Also Published As

Publication number Publication date
NO149315B (no) 1983-12-19
IL54780A0 (en) 1978-07-31
US4161599A (en) 1979-07-17
HU178316B (en) 1982-04-28
SU728717A3 (ru) 1980-04-15
YU40709B (en) 1986-04-30
IE781023L (en) 1978-12-21
AU515505B2 (en) 1981-04-09
FI63236B (fi) 1983-01-31
AT362372B (de) 1981-05-11
GR64843B (en) 1980-06-04
ATA337978A (de) 1980-10-15
IT1105427B (it) 1985-11-04
DK266978A (da) 1978-12-22
GB1584143A (en) 1981-02-04
ES469703A1 (es) 1978-12-16
IE47055B1 (en) 1983-12-14
FI63236C (fi) 1983-05-10
DE2860164D1 (en) 1980-12-18
MX5020E (es) 1983-02-22
DK147827B (da) 1984-12-17
NO149315C (no) 1984-03-28
FI781900A (fi) 1978-12-22
AU3725578A (en) 1980-01-03
NO782147L (no) 1978-12-22
DK147827C (da) 1985-06-10
BE868272A (fr) 1978-12-20
JPS6230192B2 (de) 1987-07-01
JPS549298A (en) 1979-01-24
YU135878A (en) 1982-10-31
PL113510B1 (en) 1980-12-31
IT7849919A0 (it) 1978-06-19
AR216515A1 (es) 1979-12-28
FR2395271B1 (de) 1980-04-04
PT68182A (fr) 1978-07-01
CH635588A5 (fr) 1983-04-15
IL54780A (en) 1981-01-30
LU79787A1 (fr) 1978-11-28
DD135492A5 (de) 1979-05-09
FR2395271A1 (fr) 1979-01-19
ZA783051B (en) 1979-06-27
CA1074800A (en) 1980-04-01
PL207770A1 (pl) 1979-05-07
PH17024A (en) 1984-05-11
NZ187625A (en) 1980-11-28
EP0000301A1 (de) 1979-01-10

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