DK141333B - Process for preparing tetrahydro-thieno (3,2-c) - or (2,3-c) pyridine derivatives. - Google Patents
Process for preparing tetrahydro-thieno (3,2-c) - or (2,3-c) pyridine derivatives. Download PDFInfo
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- DK141333B DK141333B DK297876AA DK297876A DK141333B DK 141333 B DK141333 B DK 141333B DK 297876A A DK297876A A DK 297876AA DK 297876 A DK297876 A DK 297876A DK 141333 B DK141333 B DK 141333B
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Description
141333141333
Opfindelsen angår en særlig fremgangsmåde til fremstilling af hidtil ukendte tetrahydro-thienof3,2-c]pyridinderivater med formlen ^Vr2 _''~~N- CH,—i/ ^7 QUi 2Λ=^3 5 eller de isomere tetrahydro-thieno[2,3-c]pyridinderivater deraf med formlen OH r2The invention relates to a particular process for the preparation of novel tetrahydro-thieno [3,2-c] pyridine derivatives of the formula: Vr 2 2,3-c] pyridine derivatives thereof of the formula OH r 2
UQ- CH2-^S^r3 iIWUQ- CH2- ^ S ^ r3 iIW
R1 hvori hydroxylgruppen OH findes i 2- eller 4-stillingen, R^-betegner et hydrogenatom eller en alkylgruppe med 1-6 carbonatnmer, 10 og R^ og R^ betegner hydrogen, halogen, en alkylgruppe med 1-6 carbonatomer eller en alkoxygruppe med 1-6 carbonato- mer, en di(C1_g-alkyl)aminogruppe eller en nitro-, cyano- eller acetamidogruppe, eller sammen med phenylkernen, 2 hvortil de er knyttet, danner en naphtylring, idet R og 3 15 R findes i 3-, 4-, 5- eller 6-stillingen, når OH findes i 2-stillingen, og findes i 3- og 5-stillingen samt er andet end hydrogen, når OH-gruppen findes it 4-stillingen.R 1 wherein the hydroxyl group OH is in the 2 or 4 position, R 2 represents a hydrogen atom or an alkyl group of 1-6 carbon atoms, and R 1 and R 2 represent hydrogen, halogen, an alkyl group of 1-6 carbon atoms or an alkoxy group. with 1-6 carbon atoms, a di (C1-6 alkyl) amino group or a nitro, cyano or acetamido group, or together with the phenyl nucleus to which they are attached form a naphthyl ring, wherein R and R -, 4-, 5- or 6-position when OH is in the 2-position and is in the 3- and 5-position and is other than hydrogen when the OH group is in the 4-position.
De omhandlede forbindelser har værdifulde terapeutiske egenskaber, idet de har antiinflammatorisk virkning, virk-20 ning som antiarrhytmika samt inhiberende virkning på blod-pladeaggregation. Forbindelserne kan derfor let anvendes til behandling af forskellige inflammationstilstande (kronisk og degenerativ rheumatisme, stomatologi, traumatologi, etc.), til behandling af forstyrrelseri hjerterytmen 141333 2 (tachycardi, extrasystoler) samt til behandling af forstyrrelser i det cerebrale og perifere kredsløb.The compounds of the invention have valuable therapeutic properties in that they have anti-inflammatory action, action as antiarrhythmic agents, and inhibitory effect on platelet aggregation. The compounds can therefore easily be used to treat various inflammatory conditions (chronic and degenerative rheumatism, stomatology, traumatology, etc.), to treat cardiac arrhythmias (tachycardia, extrasystoles) and to treat cerebral and peripheral circulatory disorders.
I beskrivelsen til dansk patent nr. 136.651 er visse 4,5,6,7-tetrahydro-thieno[3,2~c]pyridinderivater allerede blevet be-5 skrevet tilligemed en fremgangsmåde til fremstilling deraf.In the specification of Danish Patent No. 136,651, certain 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine derivatives have already been described, as well as a process for their preparation.
Den nævnte fremgangsmåde omfatter kondensation af bl.a. en forbindelse med formlen 2' hvori R er hydrogen eller halogen, med bl.a. et halogenid med 10 formlen Hal-CH2-R, hvori Hal betegner et halogenatom, og R betegner en phenylgruppe, der eventuelt er substitueret med 1-3 halogenatomer, alkylgrupper med 1-6 carbonatomer, alkoxygrupper med 1-6 carbonatomer, nitrogrupper eller hydroxygrupper, til opnåelse af et pyridiniumsalt med formlenSaid process comprises condensation of e.g. a compound of formula 2 'wherein R is hydrogen or halogen, with, inter alia, a halide of the formula Hal-CH , to give a pyridinium salt of the formula
15 R2' Xj3l_CH2-R,HaPR2 'Xj3l_CH2-R, HaP
2'2 '
hvori R , R og Hal har den ovennævnte betydning, og efterfølgende hydrogenering af nævnte pyridiniumsalt til opnåelse af et derivat med formlen Iwherein R, R and Hal have the above meaning and subsequent hydrogenation of said pyridinium salt to give a derivative of formula I
JIjO-ch -r 2' ΔJIjO-ch -r 2 'Δ
RR
ΛΛ 2 1 hvori R og R har den ovennævnte betydning. 4,5,6,7-tetra= hydro-thieno[2,3-c] pyridinderivater har også været fremstillet ved en analog fremgangsmåde (beskrivelsen til dansk patentansøgning nr. 2799/76). Denne fremgangsmåde er imidlertid dyr og kompliceret, da den kræver talrige vanskelige procedurer.ΛΛ 2 1 wherein R and R have the above meaning. 4,5,6,7-tetra = hydro-thieno [2,3-c] pyridine derivatives have also been prepared by an analogous method (the description of Danish Patent Application No. 2799/76). However, this approach is expensive and complicated as it requires numerous difficult procedures.
2 52 5
Endvidere gør anvendelsen af denne fremstillingsproces det 3 141333 vanskeligt at opnå derivater, som til nitrogenatomet har knyttet en benzylgruppe, der bærer en hydroxyIgruppe i 2-eller 4-stillingen. Til opnåelse af derivater af en sådan type ifølge nævnte fremgangsmåde er det i virkeligheden 5 nødvendigt at gå frem via det methoxylerede derivat, som derpå hydrolyseres.Furthermore, the use of this preparation process makes it difficult to obtain derivatives which have attached to the nitrogen atom a benzyl group bearing a hydroxy group at the 2 or 4 position. In order to obtain derivatives of such type according to said process, it is in fact necessary to proceed via the methoxylated derivative which is then hydrolyzed.
Det methoxylerede derivat vil kunne fremstilles i overensstemmelse med nedenstående reaktionsskema (i tilfælde af derivater af typen[3,2-c]): R1 OCH3 rsW /tvr2 10 + hvilken reaktion fører til pyridiniumderivater med formlenThe methoxylated derivative may be prepared according to the following reaction scheme (in the case of derivatives of type [3,2-c]): R1 OCH3 rsW / tvr2 + 10 which results in pyridinium derivatives of the formula
Hal9 som man kan hydrogenere til opnåelse af forbindelser med formlen R °CH3 iXi—&· 12 3 i hvilke formler R , R og R har de ovenfor anførte betydninger, som derefter kan demethyleres, f.eks. ved hjælp af 48% hydrogenbromidsyre under tilbagesvaling eller ved hjælp af pyridiniumchlorid ved 150-250°C eller ved hjælp af bortri= 20 bromid ved omgivelsernes temperatur.Hal9 which can be hydrogenated to give compounds of formula R ° CH 3 iXi - & 12 12 in which formulas R, R and R have the above meanings which can then be demethylated, e.g. using 48% hydrogen bromic acid under reflux or by pyridinium chloride at 150-250 ° C or by boron tri = 20 bromide at ambient temperature.
En sådan fremgangsmåde ville imidlertid være kostbar (som følge af de tre trin), og den ville føre til et meget lavt 141333 4 udbytte som følge af de lave udbytter ved demethyleringen/ især når methoxygruppen befinder sig i 2-stillingen på ben= zylringen.However, such a process would be costly (due to the three steps) and would result in a very low yield due to the low yields at demethylation / especially when the methoxy group is in the 2-position on the benzyl ring.
Den foreliggende opfindelse tager derfor sigte på at angive 5 en enklere fremgangsmåde til i højt udbytte at fremstille derivater med formlen la og isomere deraf med formlen Ib, i hvilke phenylkernen bærer en hydroxygruppe i 2- eller 4-stillingen.The present invention therefore aims to provide a simpler process for producing in high yield derivatives of formula Ia and isomers thereof of formula Ib in which the phenyl nucleus carries a hydroxy group at the 2 or 4 position.
Fremgangsmåden ifølge opfindelsen er ejendommelig ved, at 10 et tetrahydro-thieno[3,2-c]pyridinderivat med formlen gO^ (Ila> eller dets isomere tetrahydro[2,3-cIpyridin, med formlen di« R1 hvori R"*· har de ovenfor anførte betydninger, omsættes med 15 formaldehyd H-CHO og en phenol med formlenThe process of the invention is characterized in that a tetrahydro-thieno [3,2-c] pyridine derivative of the formula gO ^ (IIa> or its isomeric tetrahydro [2,3-cipyridine, of the formula di the above meanings are reacted with formaldehyde H-CHO and a phenol of the formula
OHOH
éc* (m) 2 3 hvori R og R har de ovenfor anførte betydninger, til opnåelse af det ønskede derivat med formlen la eller Ib.éc * (m) 23 wherein R and R have the meanings set forth above to give the desired derivative of formula Ia or Ib.
Reaktionen (af Mannichtypen) finder sted ved den ene af 20 phenolens orthostillinger, når denne er fri. Når begge orthostillingerne er optaget, finder reaktionen sted ved parastillingen.The reaction (of the Mannicht type) takes place at one of the 20 phenol ortho positions when free. When both ortho positions are occupied, the reaction takes place at the para position.
5 141333 I tilfælde af phenoler, hvori mindst en af orthostillinger-ne i forhold til OH-gruppen er fri, finder Mannichreaktio-nen således sted ved nævnte frie orthostilling, f.eks.:Thus, in the case of phenols in which at least one of the ortho positions relative to the OH group is free, the Mannich reaction takes place at said free ortho position, for example:
OKOK
l / 2-(^R1/2 - (^ R
|p-|^m r3| p- | ^ m r3
^s^A.Ri S^ s ^ A.Ri S
2 3 5 idet grupperne R og R valgfrit optager 3-, 4-, 5- eller 6-stillingen i derivatet med formlen la eller Ib.The groups R and R optionally occupy the 3-, 4-, 5- or 6-position of the derivative of formula Ia or Ib.
Den samme reaktion finder sted med usubstitueret phenol og med polycykliske phenoler, såsom eksempelvis (3-naphthol.The same reaction takes place with unsubstituted phenol and with polycyclic phenols such as, for example, (3-naphthol).
22
I tilfælde af phenoler, som bærer begge substituenterne RIn the case of phenols which carry both the substituents R
3 10 og R i orthostillingen til OH-gruppen, finder reaktionen sted ved parastillingen, f.eks.: 2 /r2 gO1·"* CHUO'"·^'3 and R in the ortho position of the OH group, the reaction takes place at the para position, for example: 2 / r 2 gO 1 ·
Kondensationsreaktionen ifølge opfindelsen udføres hensigtsmæssigt i et medium bestående af et organisk opløs-15 ningsmiddel, såsom ethanol, propanol eller dioxan. Reaktionen udføres hensigtsmæssigt i varmen ved en temperatur mellem 50° og kogepunktet for det benyttede opløsningsmiddel, idet de bedste resultater opnås ved temperaturer omkring 80°C.The condensation reaction of the invention is conveniently carried out in a medium consisting of an organic solvent such as ethanol, propanol or dioxane. The reaction is conveniently carried out in the heat at a temperature between 50 ° and the boiling point of the solvent used, with the best results being obtained at temperatures around 80 ° C.
20 Det foretrækkes at udføre reaktionen under konstant omrøring i løbet af et tidsrum på 2 til 20 timer.It is preferred to carry out the reaction with constant stirring over a period of 2 to 20 hours.
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Formaldehyd eller de forskellige polymerisationsprodukter deraf, såsom polyoxymethylen, kan anvendes til reaktionen.Formaldehyde or the various polymerization products thereof, such as polyoxymethylene, can be used for the reaction.
Rensning af det ønskede derivat udføres enten ved rekry-stallisation fra et organisk opløsningsmiddel eller efter 5 omdannelse til et salt, ved vaskning, tørring og eventuelt rekrystallisation fra et organisk opløsningsmiddel.Purification of the desired derivative is carried out either by recrystallization from an organic solvent or after conversion to a salt, by washing, drying and possibly recrystallization from an organic solvent.
De følgende eksempler illustrerer nærmere fremgangsmåden ifølge opfindelsen.The following examples further illustrate the process of the invention.
Eksempel 1 10 Fremstilling af 5-(3,5-dimethyl-4-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin.Example 1 Preparation of 5- (3,5-dimethyl-4-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno [3,2-c] pyridine.
En blanding af 4,5,6,7-tetrahydro-thieno[3,2-c]pyridin (6,1 g, 44 mmol), 2,6-dimethyl-phenol (5,4 g, 44 mmol), polyoxymethylen (2,7 g, 90 mmol) og dioxan (50 ml) omrøres 15 ved 80°C i tre timer. Efter inddampning i vakuum rekry-stalliseres resten fra ethanol-isopropanol (smeltepunkt 150°C, udbytte 48%).A mixture of 4,5,6,7-tetrahydro-thieno [3,2-c] pyridine (6.1 g, 44 mmol), 2,6-dimethyl-phenol (5.4 g, 44 mmol), polyoxymethylene (2.7 g, 90 mmol) and dioxane (50 ml) are stirred at 80 ° C for three hours. After evaporation in vacuo, the residue is recrystallized from ethanol-isopropanol (mp 150 ° C, yield 48%).
Eksempel 2Example 2
Fremstilling af 5-(2-hydroxy-5-nitro-benzyl)-6-methyl-20 4,5,6,7-tetrahydro-thieno[3,2-c]pyridin.Preparation of 5- (2-hydroxy-5-nitro-benzyl) -6-methyl-4,5,6,7,7-tetrahydro-thieno [3,2-c] pyridine.
En blanding af 6-methyl-4,5,6,7-tetrahydro-thieno[3,2-c]= pyridin (6,3 g, 41 mmol), p-nitro-phenol (5,7 g, 41 mmol), polyoxymethylen (2,5 g, 83 mmol) og dioxan (50 ml) ‘omrøres ved 80°C i fire timer. Efter inddampning i vakuum opløses 25 resten i ether og behandles med 0,5 ækvivalent oxalsyre i ethanolopløsning. Det resulterende semioxalat filtreres, vaskes med kogende methanol-vand (1:3), filtreres atter og tørres (smeltepunkt 214°C, udbytte 27%).A mixture of 6-methyl-4,5,6,7-tetrahydro-thieno [3,2-c] = pyridine (6.3 g, 41 mmol), p-nitro-phenol (5.7 g, 41 mmol) ), polyoxymethylene (2.5 g, 83 mmol) and dioxane (50 ml) are stirred at 80 ° C for four hours. After evaporation in vacuo, the residue is dissolved in ether and treated with 0.5 equivalent of oxalic acid in ethanol solution. The resulting semioxalate is filtered, washed with boiling methanol-water (1: 3), filtered again and dried (mp 214 ° C, yield 27%).
7 1413337 141333
Eksempel 3Example 3
Fremstilling af 6-(2-hydroxy-5-chlor-benzyl)-7-methyl- 4,5,6,7-tetrahydro-thieno[2,3-c]pyridin.Preparation of 6- (2-hydroxy-5-chloro-benzyl) -7-methyl-4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
En blanding af 7-methyl-4,5,6,7-tetrahydro-thieno[2,3-c]= 5 pyridin (6,0 g, 39,2 mmol), p-chlorphenol (5,05 g, 39,2 mmol), polyoxymethylen (2,36 g, 78,5 mmol) og dioxan (70 ml) omrøres ved 80°C i 15 timer. Efter inddampning i vakuum optages resten i 2N saltsyre. Den vandige fase eks-traheres med ether, gøres basisk med koncentreret ammoniak 10 og ekstraheres med methylenchlorid. De organiske ekstrakter vaskes med vand, tørres over natriumsulfat og inddamp-pes i vakuum. Resten behandles med 0,5 ækvivalent oxalsyre i ethanolopløsning. Det resulterende semioxalat filtreres og rekrystalliseres fra ethanol-dimethylformamid (smelte-15 punkt 270°C, udbytte 38%).A mixture of 7-methyl-4,5,6,7-tetrahydro-thieno [2,3-c] = 5 pyridine (6.0 g, 39.2 mmol), p-chlorophenol (5.05 g, 39 , 2 mmol), polyoxymethylene (2.36 g, 78.5 mmol) and dioxane (70 ml) are stirred at 80 ° C for 15 hours. After evaporation in vacuo, the residue is taken up in 2N hydrochloric acid. The aqueous phase is extracted with ether, made basic with concentrated ammonia 10 and extracted with methylene chloride. The organic extracts are washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is treated with 0.5 equivalent oxalic acid in ethanol solution. The resulting semioxalate is filtered and recrystallized from ethanol-dimethylformamide (m.p. 270 ° C, yield 38%).
Eksempel 4Example 4
Fremstilling af 6-(2-hydroxy-5-cyano-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin.Preparation of 6- (2-hydroxy-5-cyano-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
En blanding af 4,5,6,7-tetrahydro-thieno[2,3-c]pyridin 20 (1 g, 7,2 mmol), p-cyano-phenol (95% renhed, 0,9 g, 7,2 mmol), polyoxymethylen (0,43 g, 14,4 mmol) dg dioxan (20 ml) omrøres ved 80°C i 4 timer. Efter inddampning i vakuum optages resten i 2N saltsyre. Den vandige fase ekstraheres med ether, gøres basisk med koncentreret ammoniak 25 og ekstraheres med methylenchlorid. De organiske ekstrakter vaskes med vand, tørres over natriumsulfat og inddampes i vakuum. Resten rekrystalliseres fra isopropylether-isopropanol (smeltepunkt 134°C, udbytte 23%).A mixture of 4,5,6,7-tetrahydro-thieno [2,3-c] pyridine 20 (1 g, 7.2 mmol), p-cyano-phenol (95% purity, 0.9 g, 7), 2 mmol), polyoxymethylene (0.43 g, 14.4 mmol) dg dioxane (20 ml) is stirred at 80 ° C for 4 hours. After evaporation in vacuo, the residue is taken up in 2N hydrochloric acid. The aqueous phase is extracted with ether, made basic with concentrated ammonia 25 and extracted with methylene chloride. The organic extracts are washed with water, dried over sodium sulfate and evaporated in vacuo. The residue is recrystallized from isopropyl ether-isopropanol (mp 134 ° C, yield 23%).
**
Under anvendelse af analoge med de i de foregående eksem-30 pier beskrevne procedurer opnås følgende forbindelser: 141333 8Using analogs to the procedures described in the preceding examples, the following compounds are obtained:
Eksempel 5 5-(2-hydroxy-5-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno-[3,2-c]pyridin.Example 5 5- (2-Hydroxy-5-methoxy-benzyl) -4,5,6,7-tetrahydro-thieno- [3,2-c] pyridine.
Hvide krystaller, smeltepunkt 90°C.White crystals, m.p. 90 ° C.
5 Eksempel 6 5-(2-hydroxy-5-nitro-benzy1)-4,5,6,7-tetrahydro-thieno-[3,2-c]pyridin.Example 6 5- (2-Hydroxy-5-nitro-benzyl) -4,5,6,7-tetrahydro-thieno- [3,2-c] pyridine.
Gule krystaller, smeltepunkt 160°C.Yellow crystals, mp 160 ° C.
Eksempel 7 10 5-(2-hydroxy-3-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno- [3,2-c]pyridin.Example 7 5- (2-hydroxy-3-methoxy-benzyl) -4,5,6,7-tetrahydro-thieno- [3,2-c] pyridine.
Hvide krystaller, smeltepunkt 84°C.White crystals, mp 84 ° C.
Eksempel 8 5-(5-chlor-2-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno-15 [3,2-cjpyridin.Example 8 5- (5-Chloro-2-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno [3,2-c] pyridine.
Hvide krystaller, smeltepunkt 82-85°C.White crystals, mp 82-85 ° C.
Eksempel 9 5-(5-chlor-2-hydroxy-behzyl)-6-methyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin, semioxalat.Example 9 5- (5-Chloro-2-hydroxy-behzyl) -6-methyl-4,5,6,7-tetrahydro-thieno [3,2-c] pyridine, semioxalate.
20 Hvide krystaller, smeltepunkt 200°C.20 White crystals, m.p. 200 ° C.
Eksempel 10 5-(5-fluor-2-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno-[3,2-c]pyridin.Example 10 5- (5-Fluoro-2-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno- [3,2-c] pyridine.
Bleggule krystaller, smeltepunkt 92°C.Pale yellow crystals, melting point 92 ° C.
25 Eksempel 11 5-o-hydroxybenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridin, semioxalat.Example 11 5-o-hydroxybenzyl-4,5,6,7-tetrahydro-thieno [3,2-c] pyridine, semioxalate.
Hvide krystaller, smeltepunkt 216°C.White crystals, mp 216 ° C.
9 1413339 141333
Eksempel 12 5- (2-hydroxy-3-methyl-benzyl)-4,5,6,7-tetrahydro-thieno-[3,2-c]pyridin, semioxalat, semihydrat.Example 12 5- (2-hydroxy-3-methyl-benzyl) -4,5,6,7-tetrahydro-thieno [3,2-c] pyridine, semioxalate, semihydrate.
Hvide krystaller, smeltepunkt 198°C.White crystals, mp 198 ° C.
5 Eksempel 13 5- (3-acetamido-2-hydroxy-benzyl)-4,5,6,6-thieno[3,2-c]py= ridin.Example 13 5- (3-Acetamido-2-hydroxy-benzyl) -4,5,6,6-thieno [3,2-c] pyridine.
Hvide krystaller, smeltepunkt 154°C.White crystals, mp 154 ° C.
Eksempel 14 10 6-(5-chlor-2-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno- [2,3-c]pyridin.Example 14 6- (5-Chloro-2-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
Hvide krystaller, smeltepunkt 222°C.White crystals, mp 222 ° C.
Eksempel 15 6- (3,4-dichlor-2-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno- 15 [2,3-c]pyridin.Example 15 6- (3,4-Dichloro-2-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
Hvide krystaller, smeltepunkt 153°C.White crystals, mp 153 ° C.
Eksempel 16 6-(2-hydroxy-5-nitro-benzyl)-4,5,6,7-tetrahydro-thieno-[2,3-c]pyridin.Example 16 6- (2-hydroxy-5-nitro-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
20 Gule krystaller, smeltepunkt 159°C.Yellow crystals, mp 159 ° C.
Eksempel 17 6-(3,5-dimethyl-4-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin.Example 17 6- (3,5-Dimethyl-4-hydroxy-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
Elfenbensfarvede krystaller, smeltepunkt 118°C.Ivory crystals, m.p. 118 ° C.
25 Eksempel 18 6-(2-hydroxy-3-isopropyl-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridin.Example 18 6- (2-hydroxy-3-isopropyl-benzyl) -4,5,6,7-tetrahydro-thieno [2,3-c] pyridine.
Meget blege, gule krystaller, smeltepunkt 101°C.Very pale yellow crystals, melting point 101 ° C.
Claims (4)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7521549 | 1975-07-09 | ||
| FR7521549A FR2317303A1 (en) | 1975-07-09 | 1975-07-09 | PROCESS FOR PREPARING TETRAHYDROTHIENO (3,2-C) AND (2,3-C) PYRIDINE DERIVATIVES |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK297876A DK297876A (en) | 1977-01-10 |
| DK141333B true DK141333B (en) | 1980-02-25 |
| DK141333C DK141333C (en) | 1980-08-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK297876AA DK141333B (en) | 1975-07-09 | 1976-07-01 | Process for preparing tetrahydro-thieno (3,2-c) - or (2,3-c) pyridine derivatives. |
Country Status (26)
| Country | Link |
|---|---|
| JP (1) | JPS5236691A (en) |
| AR (1) | AR211019A1 (en) |
| AT (1) | AT348526B (en) |
| BE (1) | BE843822A (en) |
| CA (1) | CA1071634A (en) |
| CH (1) | CH609349A5 (en) |
| DD (1) | DD125081A5 (en) |
| DE (1) | DE2630474A1 (en) |
| DK (1) | DK141333B (en) |
| ES (1) | ES448404A1 (en) |
| FR (1) | FR2317303A1 (en) |
| GB (1) | GB1544093A (en) |
| GR (1) | GR59812B (en) |
| HU (1) | HU172280B (en) |
| IE (1) | IE42821B1 (en) |
| IL (1) | IL49641A (en) |
| LU (1) | LU74674A1 (en) |
| MX (1) | MX3224E (en) |
| NL (1) | NL7605362A (en) |
| PH (1) | PH12311A (en) |
| PL (1) | PL100685B1 (en) |
| PT (1) | PT65072B (en) |
| SE (1) | SE421699B (en) |
| SU (1) | SU628819A3 (en) |
| YU (1) | YU40137B (en) |
| ZA (1) | ZA763219B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5665315A (en) * | 1979-11-02 | 1981-06-03 | Nec Corp | Magnetic recording and inspecting system |
| DE3736664A1 (en) * | 1987-10-29 | 1989-05-11 | Boehringer Ingelheim Kg | TETRAHYDRO-FURO- AND -THIENO (2,3-C) PYRIDINE, THEIR USE AS A MEDICAMENT AND METHOD FOR THE PRODUCTION THEREOF |
| NZ233654A (en) * | 1989-05-18 | 1993-02-25 | Bristol Myers Squibb Co | 2-aminomethyl-5-aminophenol derivatives; hair dye compositions containing them |
-
1975
- 1975-07-09 FR FR7521549A patent/FR2317303A1/en active Granted
-
1976
- 1976-03-31 LU LU74674A patent/LU74674A1/xx unknown
- 1976-04-01 CH CH404576A patent/CH609349A5/en not_active IP Right Cessation
- 1976-04-21 GR GR50593A patent/GR59812B/en unknown
- 1976-04-23 YU YU1030/76A patent/YU40137B/en unknown
- 1976-05-06 PT PT65072A patent/PT65072B/en unknown
- 1976-05-19 NL NL7605362A patent/NL7605362A/en not_active Application Discontinuation
- 1976-05-21 IE IE1079/76A patent/IE42821B1/en unknown
- 1976-05-24 IL IL49641A patent/IL49641A/en unknown
- 1976-05-31 ES ES448404A patent/ES448404A1/en not_active Expired
- 1976-06-01 ZA ZA763219A patent/ZA763219B/en unknown
- 1976-06-03 AR AR263501A patent/AR211019A1/en active
- 1976-06-09 SU SU762366005A patent/SU628819A3/en active
- 1976-06-10 CA CA254,573A patent/CA1071634A/en not_active Expired
- 1976-06-16 MX MX000320U patent/MX3224E/en unknown
- 1976-07-01 DK DK297876AA patent/DK141333B/en not_active IP Right Cessation
- 1976-07-01 PH PH7618641A patent/PH12311A/en unknown
- 1976-07-05 AT AT489876A patent/AT348526B/en not_active IP Right Cessation
- 1976-07-06 BE BE168664A patent/BE843822A/en not_active IP Right Cessation
- 1976-07-07 DE DE19762630474 patent/DE2630474A1/en active Pending
- 1976-07-07 DD DD193745A patent/DD125081A5/xx unknown
- 1976-07-07 SE SE7607762A patent/SE421699B/en not_active IP Right Cessation
- 1976-07-08 JP JP51081441A patent/JPS5236691A/en active Granted
- 1976-07-08 GB GB28511/76A patent/GB1544093A/en not_active Expired
- 1976-07-08 PL PL1976191016A patent/PL100685B1/en unknown
- 1976-07-09 HU HU76PA00001255A patent/HU172280B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB1544093A (en) | 1979-04-11 |
| PT65072A (en) | 1976-06-01 |
| JPS5310077B2 (en) | 1978-04-11 |
| LU74674A1 (en) | 1976-09-01 |
| GR59812B (en) | 1978-03-01 |
| SU628819A3 (en) | 1978-10-15 |
| NL7605362A (en) | 1977-01-11 |
| DE2630474A1 (en) | 1977-01-13 |
| HU172280B (en) | 1978-07-28 |
| MX3224E (en) | 1980-07-28 |
| IL49641A (en) | 1978-08-31 |
| IE42821L (en) | 1977-01-09 |
| CA1071634A (en) | 1980-02-12 |
| YU103076A (en) | 1982-02-28 |
| CH609349A5 (en) | 1979-02-28 |
| ZA763219B (en) | 1977-05-25 |
| PT65072B (en) | 1977-09-13 |
| AU1568676A (en) | 1977-03-31 |
| IE42821B1 (en) | 1980-10-22 |
| SE421699B (en) | 1982-01-25 |
| PH12311A (en) | 1979-01-16 |
| FR2317303B1 (en) | 1977-12-16 |
| BE843822A (en) | 1977-01-06 |
| DD125081A5 (en) | 1977-03-30 |
| DK297876A (en) | 1977-01-10 |
| ES448404A1 (en) | 1977-07-01 |
| DK141333C (en) | 1980-08-25 |
| YU40137B (en) | 1985-08-31 |
| PL100685B1 (en) | 1978-10-31 |
| SE7607762L (en) | 1977-01-10 |
| JPS5236691A (en) | 1977-03-22 |
| FR2317303A1 (en) | 1977-02-04 |
| AT348526B (en) | 1979-02-26 |
| AR211019A1 (en) | 1977-10-14 |
| ATA489876A (en) | 1978-07-15 |
| IL49641A0 (en) | 1976-07-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |