DE2238054C3 - O-dimethylaminoethyl-acyloxy- (or -alkoxycarbonyloxy-) thymoles and process for their preparation - Google Patents
O-dimethylaminoethyl-acyloxy- (or -alkoxycarbonyloxy-) thymoles and process for their preparationInfo
- Publication number
- DE2238054C3 DE2238054C3 DE19722238054 DE2238054A DE2238054C3 DE 2238054 C3 DE2238054 C3 DE 2238054C3 DE 19722238054 DE19722238054 DE 19722238054 DE 2238054 A DE2238054 A DE 2238054A DE 2238054 C3 DE2238054 C3 DE 2238054C3
- Authority
- DE
- Germany
- Prior art keywords
- dimethylamine
- ethyl
- dimethylaminoethyl
- acyloxy
- thymoles
- 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
- 238000000034 method Methods 0.000 title description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 229930007823 thymol Natural products 0.000 title description 2
- 125000003639 thymyl group Chemical group C1(=CC(C)=CC=C1C(C)C)* 0.000 title description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- ROSDSFDQCJNGOL-UHFFFAOYSA-N dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Chemical compound [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- -1 alkali metal salt Chemical class 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- 230000000875 corresponding Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- VRYMTAVOXVTQEF-UHFFFAOYSA-N Moxisylyte Chemical compound CC(C)C1=CC(OC(C)=O)=C(C)C=C1OCCN(C)C VRYMTAVOXVTQEF-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229960003509 Moxisylyte Drugs 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000004429 atoms Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000004432 carbon atoms Chemical group C* 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 230000001225 therapeutic Effects 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- IKMJGHPYOYVETB-UHFFFAOYSA-N 1,4-dioxane;ethyl acetate Chemical compound CCOC(C)=O.C1COCCO1 IKMJGHPYOYVETB-UHFFFAOYSA-N 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N Chlormethine Chemical group ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000903 blocking Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 230000000916 dilatatory Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drugs Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral Effects 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- NBEOBNPETXOCKI-UHFFFAOYSA-N propan-2-ylchloranuidyl formate Chemical compound CC(C)[Cl-]OC=O NBEOBNPETXOCKI-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002441 reversible Effects 0.000 description 1
- 150000003388 sodium compounds Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Description
'S'S
in der R eine Alkylgruppe mit 4 bis 11 C-Atomen odereineAlkoxygruppeR'Omit3bis IOC-Atomen ist, und ihre pharmazeutisch verträglichen Salze.in which R is an alkyl group with 4 to 11 carbon atoms or an alkoxy group R'O with 3 to IOC atoms and their pharmaceutically acceptable salts.
2. [/>'-(4-Isovaleryloxy(hymoxy)-äthyl]-dimethy/-amin. 2. [/> '- (4-Isovaleryloxy (hymoxy) ethyl] dimethylamine.
3. [^-H-CapronyloxythymoxyHithyn-dimcthylaniin. 3. [^ -H-CapronyloxythymoxyHithyn-dimethylaniine.
4. [/>'-(4-Capryloxythymoxy)-Uthyl]-dimethylamin. 4. [/> '- (4-Capryloxythymoxy) -utyl] -dimethylamine.
5. |j/-(4-Caprinyloxythymoxy)-äthyl]-dimethyluniin. 5. | j / - (4-caprinyloxythymoxy) ethyl] dimethylunine.
6. [/)'-(4-Isopropoxycarbonyloxythymoxy)-äthyl]-dimethylamin. 6. [/) '- (4-Isopropoxycarbonyloxythymoxy) ethyl] dimethylamine.
7. Verfahren zur Herstellung von Verbindungen der allgemeinen Forme! I, in der R die obengenannte Bedeutung hat, dadurch gekennzeichnet, daß man die Verbindung II in an sich bekannter Weise7. Process for the preparation of compounds of the general form! I, in the R the above Has meaning, characterized in that the compound II is known per se
(H)(H)
N(CH3)N (CH 3 )
3535
4040
mit dem Anhydrid der entsprechenden Alkancarbonsäure in Pyridin oder Chinolin ein bis mehrere Stunden auf 100 bis 1700C erhitzt, oder indem man in an sich bekannter Weise die Verbindung II in Tetrahydrofuran, gegebenenfalls in Gegenwart von Dimethylformamid oder Dimethyllulfoxid, mit Natriumhydrid oder Alkalimetalltlkoholat in ihr Alkalimetallsalz überführt und dieses in Suspension mit dem entsprechenden Alkancarbonsäurechlorid oder Alkoxycarbonylchlorid 2 bis 6 Stunden auf 40 bis 8O0C erwärmt.with the anhydride of the corresponding alkanecarboxylic acid in pyridine or quinoline for one to several hours at 100 to 170 0 C, or by heating the compound II in tetrahydrofuran, optionally in the presence of dimethylformamide or dimethyl sulfoxide, with sodium hydride or alkali metal alcoholate in it Converted alkali metal salt and heated this in suspension with the corresponding alkanecarboxylic acid chloride or alkoxycarbonyl chloride to 40 to 80 0 C for 2 to 6 hours.
Aus der Gruppe der basisch substituierten Thymoläther konnte bis jetzt nur ein Produkt, das [>-(4-Acetoxythymoxy)-äthyl]-dimethylamin (WHO-Freiname »Moxisylyt«) als Therapeutikum in begrenztem Umfang bei peripheren Durchblutungsstörungen Bedeutung gewinnen. Es hat nicht an Versuchen gefehlt, die pharmazeutischen Nachteile dieser Substanz, wie geringe Resorbierbarkeit, kurze Wirkungsdauer, rela-From the group of the basic substituted thymol ethers only one product, the [> - (4-acetoxythymoxy) ethyl] dimethylamine, could be used up to now (WHO non-proprietary name »Moxisylyt«) as a therapeutic agent to a limited extent in the case of peripheral circulatory disorders to win. There has been no lack of attempts to discover the pharmaceutical disadvantages of this substance, such as low absorbability, short duration of action, rela-
60 tive Toxizität und Instabilität, zu beheben (s. zum Beispiel Arzneimittelforschung 17,305 bis 309 [1967]), doch die einzigen, durch Molekülmanipulationen erhaltenen wirksamen Derivate konnten auf Grund ihrer Halogenalkylamin-(N-Lost-)-Funktion keinen Eingang in die Therapie finden. 60 tive toxicity and instability (see, for example, drug research 17,305 to 309 [1967]), but the only effective derivatives obtained through molecular manipulation could not be used in therapy due to their haloalkylamine (nitrogen mustard) function Find.
In dem Bemühen, neue peripher dilatierende Moxisylyt-Abkömmlinge mit verbesserten Eigenschaften zu entwickeln, wurde überraschenderweise gefunden, daß Verbindungen der allgemeinen Formel IIn an effort to find new peripherally dilating moxisylyte derivatives with improved properties To develop, it was surprisingly found that compounds of general formula I
O—(CH2),- N(CH3),O— (CH 2 ), - N (CH 3 ),
CH,CH,
in der R eine Alkylgruppe mit 4 bis 11 C-Atomen odcreineAlkoxygruppeR' — Omit 3bis IOC-Atomen ist, und ihre pharmazeutisch unbedenklichen Salze diese Eigenschaften aufweisen.in which R is an alkyl group with 4 to 11 carbon atoms or a pure alkoxy group R '- O with 3 to IOC atoms is, and their pharmaceutically acceptable salts have these properties.
Als Beispiele typischer Verbindungen der Formel I seien genannt:Examples of typical compounds of the formula I include:
[/i-(4-Isopropoxycarboxythymoxy)-äthyl]-[/ i- (4-Isopropoxycarboxythymoxy) ethyl] -
dimethylamin,
[/)-(4-Capronyloxythymoxy)-äthy!]-dimethylamine,
[/) - (4-Capronyloxythymoxy) -ethy!] -
dimcthylamin,
[//-(4-Isovaleryloxythymoxy)-äthyl]-dimethylamine,
[// - (4-Isovaleryloxythymoxy) ethyl] -
dimclhylamin,
[/H4-Capryloxythymoxy)-äthyl]-dimethylamine,
[/ H4-Capryloxythymoxy) ethyl] -
dimethylamin,
[,'(-(4-Caprinyloxythymoxy)-äthyl]-dimethylamine,
[, '(- (4-Caprinyloxythymoxy) ethyl] -
dimethylamin,
rj/-(4-Laurinyloxythymoxy)-äthy!]-dimethylamine,
rj / - (4-laurinyloxythymoxy) -ethy!] -
dimethylamin,
[/i-(4-Isocaprinyloxythymoxy)-;ithyl]-dimethylamine,
[/ i- (4-isocaprinyloxythymoxy) -; ithyl] -
dimethylamin
und die Salze dieser Verbindungen.dimethylamine
and the salts of these compounds.
Die Verbindungen der Formel I können nach an sich bekannten Verfahren hergestellt werden —- wobei man jedoch wegen der großen sterischen Hinderung besondere Techniken anwenden muß -— beispielsweise, indem man die Verbindung IIThe compounds of the formula I can be prepared by processes known per se - wherein however, because of the great steric hindrance, special techniques must be used - for example, by connecting the connection II
HOHO
(II)(II)
L JUo-(CH2J2-N(CH3).L JUo- (CH 2 J 2 -N (CH 3 ).
mit dem Anhydrid der entsprechenden Alkancarbonsäurc in Pyridin oder Chinolin ein bis mehrere Stunden auf 100 bis 170° C, vorzugsweise 130 bis 150° C, erhitzt oder indem man die Verbindung II in Tetrahydrofuran, gegebenenfalls in Gegenwart von Dimethylformamid oder Dimethylsulfoxid, mit Natriumhydrid oder Alkalimetalialkoholat in ihr Alkalimetallsalz überführt und dieses in Suspension mit dem entsprechenden Alkancarbonsäurechlorid oder Alkoxv-with the anhydride of the corresponding alkanecarboxylic acid in pyridine or quinoline for one to several hours at 100 to 170 ° C, preferably 130 to 150 ° C, heated or by the compound II in tetrahydrofuran, optionally in the presence of dimethylformamide or dimethyl sulfoxide, with sodium hydride or alkali metal alcoholate in its alkali metal salt transferred and this in suspension with the corresponding alkanecarboxylic acid chloride or Alkoxv-
carbonylchlorid 2 bis 6 Stunden auf 40 bis SO C erwärmt.carbonyl chloride at 40 to SO C for 2 to 6 hours warmed up.
Die erfinuungsgcmäßen Substanzen zeichnen sich — im Gegensatz zum Moxisylyt — dadurch aus, daß sie bereits in niedriger Dosierung auch bei pei oraler Anwendung eine typische ^-Rezeptoren blockierende Wirkung besitzen, wie mit Hilfe von Adrenalinumkehrversuchen nachgewiesen werden konnte. Damit sind die Voraussetzungen für die gewünschte, therapeutisch außerordentlich nützliche peripher diialierende Wirkung bei oraler Applikation erfüllt.The substances according to the invention stand out - in contrast to Moxisylyt - by the fact that it is already in low dosage even with pei oral Application have a typical ^ -receptor blocking effect, such as with the help of adrenaline reversal experiments could be proven. Thus, the prerequisites for the desired, therapeutic extremely useful peripherally dialing effect met when administered orally.
Die Verbindung 11 kann durch schonende Hydrolyse technischen Moxisylyts oder durch Diazotierung und Verkochung des aus dem Thymyl-fi'-dimethylaminoäthyläther durch Nitrosierung und Reduktion leicht zugänglichen 4-Aininoderivates hergestellt werden.The compound 11 can by gentle hydrolysis technical moxisylyts or by diazotization and boiling of the thymyl-fi'-dimethylaminoethyl ether easily accessible 4-amino derivatives can be produced by nitrosation and reduction.
Auf Grund ihres günstigen therapeutischen Quotienten können die erfindungsgemäßen neuen Thymolderivate unbedenklich als solche oder in Form von · pharmazeutischen Zubereitungen in Mischung mit geeigneten und üblichen Träger- oder Hilfsstoffen in oraler, subkutaner, intravenöser und anderer Weise appliziert werden. Als pharmazeutische Zubereitungen kommen Tabletten. Kapseln, Dragees, Suspensionen und Suppositorien in Frage. Die Einzeldosis der 25 g Derivate liegt je nach Indikation im Bereich von 2 bis 50 mc. vorzucswcise um 10 mc.Because of their favorable therapeutic quotient, the new thymol derivatives according to the invention can harmless as such or in the form of pharmaceutical preparations mixed with suitable and customary carriers or excipients in oral, subcutaneous, intravenous and other ways be applied. Tablets are used as pharmaceutical preparations. Capsules, coated tablets, suspensions and suppositories in question. The single dose of the 25 g derivatives is in the range from 2 to, depending on the indication 50 mc. advance by 10 mc.
Ausbeute 37 g (60% der Theorie) vom Schmp. 177 bis 178 C (aus Isopropanol).Yield 37 g (60% of theory) with a melting point of 177 up to 178 C (from isopropanol).
3. [/M4-Capryloxythymoxy)-äthyl]-dimethylamin · HCl3. [/ M4-capryloxythymoxy) ethyl] dimethylamine · HCl
Zu einer Suspension von 4 g NaH (50%ig) in 90 m! trockenem THF und 30 ml DMF wird eine Lösung von 17 g Ii in 90 ml THF getropft. Nach Beendigung der Wasserstoffentwicklung fügt man 13,1 g Caprylsäurechlorid, gelöst in 30 ml THF, hinzu und erhitzt 3 Stunden auf 65''C. Danach wird das Lösungsmittel im Vakuum abdestilliert und der Rückstand zwischen Wasser und Äther verteilt. Aus der getrockneten Ätherphase fällt man das Hydrochlorid mit HCl-Gas. Es wird aus Isopropanol umkristallisiert.To a suspension of 4 g NaH (50%) in 90 m! dry THF and 30 ml DMF becomes a solution dropped from 17 g of Ii in 90 ml of THF. When the evolution of hydrogen has ended, 13.1 g of caprylic acid chloride are added, dissolved in 30 ml of THF, added and heated to 65''C for 3 hours. After that the solvent distilled off in vacuo and the residue partitioned between water and ether. From the dried In the ether phase, the hydrochloride is precipitated with HCl gas. It is recrystallized from isopropanol.
Ausbeute 11,7 g (47% der Theorie) vom Schmp. 163 bis 164 CYield 11.7 g (47% of theory) with a melting point of 163 up to 164 C
4. [//-(4-Caprinyloxythymoxy)-äthyl]-dimethylamin · HCl4. [// - (4-Caprinyloxythymoxy) ethyl] dimethylamine · HCl
22,5 g II werden analog 3 in das Natriumsalz übergeführt und mit 18,2 g Caprinsäurechlorid in THF/ DMSO (10:1) kondensiert. Erhitzungszeit: 1,5 Stunden, Temperatur 70 C. Es wird wie beschrieben aufgearbeitet. 22.5 g II are converted into the sodium salt analogously to 3 and condensed with 18.2 g of capric acid chloride in THF / DMSO (10: 1). Heating time: 1.5 hours, Temperature 70 ° C. It is worked up as described.
Ausbeute 27.4 g (64% der Theorie) vom Schmp. 157 bis 158 C (aus n-Butanol).Yield 27.4 g (64% of theory) with a melting point of 157 up to 158 C (from n-butanol).
Beispiele
(alle Produkte gaben korrekte Elemenlaranalysen)Examples
(all products gave correct element analysis)
1. r,;-(4-lsovaleryloxythymoxy)-äthyI]-1. r, ;-( 4-isovaleryloxythymoxy) -ethyI] -
dimethylamin · HCldimethylamine · HCl
31 g II werden in 60 ml über KOH getrocknetem Pyridin aufgenommen, mit 54,2 g Isovalcriansäureanhydrid versetzt und 4 Stunden auf 140 C erhitzt.31 g of II are taken up in 60 ml of pyridine dried over KOH, with 54.2 g of isovalcric anhydride added and heated to 140 C for 4 hours.
Anschließend destilliert man im Vakuum den Überschuß an Pyridin und Anhydrid ab, nimmt den Rückstand in Äther auf, filtriert und leitet HCl-Gas ein. Das rohe Hydrochlorid wird aus Äthylacctat-Dioxan umkristallisiert.The excess pyridine and anhydride are then distilled off in vacuo and the The residue is dissolved in ether, filtered and HCl gas is passed in. The crude hydrochloride is made from ethyl acetate-dioxane recrystallized.
Ausbeute 43,0 a, (82,6% der Theorie).Yield 43.0 a, (82.6% of theory).
Schmp. 182 bis"!83 C.M.p. 182 to "! 83 C.
2. [/H4-Capronyloxythymoxy)-äthyl]-2. [/ H4-Capronyloxythymoxy) ethyl] -
dimethylamin · HCldimethylamine · HCl
45 g Il werden mit 85,6 gCapronsäureanhydrid und 80 g Pyridin 5 Stunden auf 130 C erhitzt. Es wird wie unter I beschrieben weiter verfahren.45 g of II with 85.6 g of caproic anhydride and 80 g of pyridine heated to 130 ° C. for 5 hours. Proceed as described under I.
5. [//-(4-Isopropoxycarbonyloxythymoxy)-äthyl]-dimethylamin · HCl5. [// - (4-Isopropoxycarbonyloxythymoxy) ethyl] dimethylamine · HCl
Eine Suspension von 6,98 g NaH (50%ig) in 100 ecm trockenem Tetrahydrofuran wird vorgelegt und tropfenweise mit einer Lösung von 34,4 g II in 100 ecm THF unter Kühlung versetzt. Es wird 30 Minuten bei 60 bis 70"C gerührt und die Lösung der Natriumverbindung abgekühlt. Anschließend tropft man bei 30 bis 400C eine Lösung von 35 g Chlorameisensäureisopropylester in etwas THF zu und erhitzt 2 Stunden unier Rückfluß. Es wird im Vakuum eingedampft und der Rückstand in verdünnter Salzsäure aufgenommen. Man destilliert im Vakuum zur Trockne und nimmt den Rückstand mit 200 ecm siedendem Isopropanol auf, kühlt ab und filtriert. Das Filtrat wird im Vakuum eingeengt und der ölige Rückstand mit THF zur Kristallisation gebracht.A suspension of 6.98 g of NaH (50%) in 100 ecm of dry tetrahydrofuran is initially introduced and a solution of 34.4 g of II in 100 ecm of THF is added dropwise with cooling. It is stirred for 30 minutes at 60 to 70 "C and the solution cooled the sodium compound. Then added dropwise at 30 to 40 0 C a solution of 35 g of isopropyl chloroformate in some THF and heated for 2 hours unier reflux. The mixture is evaporated in vacuo and The residue is taken up in dilute hydrochloric acid, it is distilled to dryness in vacuo and the residue is taken up in 200 ml of boiling isopropanol, cooled and filtered, the filtrate is concentrated in vacuo and the oily residue is crystallized with THF.
Ausbeute 20.8 g (aus Toluol) vom Schmp. 180 bis 181 C.Yield 20.8 g (from toluene) with a melting point of 180 to 181 C.
Claims (1)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19722238054 DE2238054C3 (en) | 1972-08-02 | O-dimethylaminoethyl-acyloxy- (or -alkoxycarbonyloxy-) thymoles and process for their preparation | |
| DK339473A DK138316C (en) | 1972-08-02 | 1973-06-19 | ANALOGICAL PROCEDURE FOR THE PREPARATION OF ESTERS OF (BETA- (4-HYDROXY-THYMOXY) ETHYL) DIMETHYLAMINE OR ACID ADDITIONAL SALTS THEREOF |
| AU57080/73A AU471360B2 (en) | 1972-08-02 | 1973-06-19 | Thymol derivatives anda process for their preparation |
| GB3179673A GB1374396A (en) | 1972-08-02 | 1973-07-04 | Thymol derivatives |
| JP7923573A JPS52940B2 (en) | 1972-08-02 | 1973-07-13 | |
| FR7327251A FR2194427B1 (en) | 1972-08-02 | 1973-07-25 | |
| CA177,846A CA1030155A (en) | 1972-08-02 | 1973-08-01 | Thymol derivatives and a process for their preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19722238054 DE2238054C3 (en) | 1972-08-02 | O-dimethylaminoethyl-acyloxy- (or -alkoxycarbonyloxy-) thymoles and process for their preparation |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2238054A1 DE2238054A1 (en) | 1974-02-21 |
| DE2238054B2 DE2238054B2 (en) | 1975-07-24 |
| DE2238054C3 true DE2238054C3 (en) | 1976-03-11 |
Family
ID=
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