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 PDFInfo
- 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
- Authority
- EP
- European Patent Office
- Prior art keywords
- acid
- formula
- thieno
- derivatives
- carboxy
- 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.)
- Expired
Links
- 0 *c(nc1)cc2c1[s]cc2 Chemical compound *c(nc1)cc2c1[s]cc2 0.000 description 1
Classifications
-
- 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%.
Landscapes
- 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
worin R Wasserstoff oder Carboxyl bedeutet, dadurch gekennzeichnet, dass man eine Verbindung der Formel
mit salpetriger Säure umsetzt und die so erhaltenen Verbindungen der Formel
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.
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
ID=9192350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE816390A (en) * | 1973-06-15 | 1974-12-16 | Vinyl or ethynyl-substd. mercapto-methyl pyridines - for treatment of rheumatoid arthritis and inflammatory troubles | |
| 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 |
| ES2153434T3 (es) * | 1994-02-02 | 2001-03-01 | Lilly Co Eli | Inhibidores de la proteasa del vih y sus intermedios. |
| 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)
| 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 |
-
1977
- 1977-06-21 FR FR7718991A patent/FR2395271A1/fr active Granted
-
1978
- 1978-05-05 GR GR56151A patent/GR64843B/el unknown
- 1978-05-10 AT AT337978A patent/AT362372B/de not_active IP Right Cessation
- 1978-05-11 ES ES469703A patent/ES469703A1/es not_active Expired
- 1978-05-22 CH CH554378A patent/CH635588A5/fr not_active IP Right Cessation
- 1978-05-23 IE IE1023/78A patent/IE47055B1/en unknown
- 1978-05-23 US US05/908,857 patent/US4161599A/en not_active Expired - Lifetime
- 1978-05-24 IL IL54780A patent/IL54780A/xx unknown
- 1978-05-29 ZA ZA00783051A patent/ZA783051B/xx unknown
- 1978-05-30 AR AR272375A patent/AR216515A1/es active
- 1978-05-30 GB GB24217/78A patent/GB1584143A/en not_active Expired
- 1978-06-07 YU YU1358/78A patent/YU40709B/xx unknown
- 1978-06-08 LU LU79787A patent/LU79787A1/xx unknown
- 1978-06-12 MX MX787139U patent/MX5020E/es unknown
- 1978-06-13 DE DE7878400018T patent/DE2860164D1/de not_active Expired
- 1978-06-13 EP EP78400018A patent/EP0000301B1/de not_active Expired
- 1978-06-14 DK DK266978A patent/DK147827C/da not_active IP Right Cessation
- 1978-06-14 FI FI781900A patent/FI63236C/fi not_active IP Right Cessation
- 1978-06-15 DD DD78206026A patent/DD135492A5/de not_active IP Right Cessation
- 1978-06-15 PH PH21265A patent/PH17024A/en unknown
- 1978-06-16 PT PT68182A patent/PT68182A/pt unknown
- 1978-06-16 CA CA305,665A patent/CA1074800A/en not_active Expired
- 1978-06-19 AU AU37255/78A patent/AU515505B2/en not_active Expired
- 1978-06-19 IT IT49919/78A patent/IT1105427B/it active
- 1978-06-20 BE BE188692A patent/BE868272A/xx not_active IP Right Cessation
- 1978-06-20 JP JP7479778A patent/JPS549298A/ja active Granted
- 1978-06-20 PL PL1978207770A patent/PL113510B1/pl unknown
- 1978-06-20 HU HU78PA1320A patent/HU178316B/hu not_active IP Right Cessation
- 1978-06-20 NO NO782147A patent/NO149315C/no unknown
- 1978-06-20 NZ NZ187625A patent/NZ187625A/xx unknown
- 1978-06-21 SU SU782627501A patent/SU728717A3/ru active
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