CH367828A - Process for the preparation of a new iminodibenzyl derivative - Google Patents
Process for the preparation of a new iminodibenzyl derivativeInfo
- Publication number
- CH367828A CH367828A CH6095558A CH6095558A CH367828A CH 367828 A CH367828 A CH 367828A CH 6095558 A CH6095558 A CH 6095558A CH 6095558 A CH6095558 A CH 6095558A CH 367828 A CH367828 A CH 367828A
- Authority
- CH
- Switzerland
- Prior art keywords
- iminodibenzyl
- parts
- derivative
- new
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- ZSMRRZONCYIFNB-UHFFFAOYSA-N 6,11-dihydro-5h-benzo[b][1]benzazepine Chemical class C1CC2=CC=CC=C2NC2=CC=CC=C12 ZSMRRZONCYIFNB-UHFFFAOYSA-N 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 4
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229910052987 metal hydride Inorganic materials 0.000 claims 1
- 150000004681 metal hydrides Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 201000003102 mental depression Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung eines neuen Iyninodibenzylderivates Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung eines neuen Derivates des Iminod'ibenzyls mit wertvollen pharmakologischen Ei genschaften.
Es wurde überraschenderweise gefunden, dass das bisher nicht bekanntgewordene 5-(a-Dimethylamino- methyl-äthyl)-iminodibenzyl (5-[a-Dimethylamino- methyl-äthyl]-10,11-dihydro-5-dibenzo[b,f]azepin) der Formel
EMI0001.0014
die sedative Wirkung seiner bekannten Isomeren und Homologen erheblich zu steigern vermag.
Es eignet sich insbesondere in Kombination mit dem isomeren 5-(/3-Dimethylamino-propyl) imnodibenzyl oder 5- (y-Dimethylamino-propyl)4iminodibenzyl zur Behand lung von gewissen Formen von Geisteskrankheiten, vor allem Gemütsdepressionen, wobei sich solche Kombinationen durch gute therapeutische Wirkung und das Fehlen vegetativer Nebenwirkungen aus zeichnen.
Das erfindungsgemässe Verfahren zur Herstellung einer Verbindung der Formel I ist dadurch gekenn zeichnet, d'ass man ein a-Halogen-propionsäure-dime- thylamid, insbesondere a-Brom-propionsäuredimethyl- amid, mit Iminodibenzyl in Gegenwart eines säure bindenden Mittels oder mit einem Salz des Imino- dibenzyls umsetzt und das erhaltene 5-(a-Dimethyl- carbamyl-äthyl)
-iminodibenzyl mit einem Alkah.- metall-ErdmetaEhydrid', insbesondiere Uthiumal'umi- niumhyd'rid, reduziert.
Im nachfolgenden Beispiel bedeuten Teile Ge wichtsteile, diese verhalten sich zu Volumteilen wie g zu cms. Die Temperaturen sind in Celsiusgraden angegeben.
<I>Beispiel</I> 40 Teile Iminod'ibenzyl werden in 150 Volum teilen Benzol und 50 Volumteilen Tolluol .gelöst.
Bei 40-50- werden unter Rühren und Einleiten von Stickstoff 40 Teile Natriumamid in Toluoi zugetropft. Nach der Zugabe von Natriumamid wird das Ganze eine Stunde unter Rückfluss gekocht.
Dann wird es auf -15 abgekühlt und 20 Teile a-Brompropion- säure-dimethylamid und 20 Teile Toluol werden so zugetropft,
dass die Reaktionstemperatur zwischen -10 bis 8 gehalten werden kann. Anschliessend rührt man das Reaktionsgemisch eine Stunde bei Raum temperatur weiter und kocht es hierauf drei Stunden unter Rückfluss. Man kühlt es .ab, saugt vom aus geschiedenen Natriumbromid ab und destilliert das Filtrat im Hochvakuum im Hickmann-Kolben,
wo bei man das 5-(a-Dimethylcarbamyl:-äthyi)-imino- dibenzyl erhält. F: 114-116 (Äther).
30 Teile Lithiumaluminiumhydrid werden in 2000 Volumteilen abs. Ather suspendiert und innerhalb 11/2 Stunden untern Rühren 240 Teile des oben er haltenen Ami.des in 720 Vdlumteillen Tetrahydrofuran zugetropft, wobei:
die Temperatur auf etwa<B>381></B> steigt. Man erwärmt anschliessend drei Stunden am Rück fluss, kühlt dann auf -10 ab und zersetzt das. Re aktionsgemisch mit Wasser.
Die ätherische Phase wird 4-5mal mit je 200 Vo- lumteilen 2-n Salzsäure ausgezogen. Die sauren Aus- züge werden mit konz. Natronlauge alkalisch ge stellt und das ausgeschiedene Öl in Äther aufge nommen.
Die ätherische Lösung wird mit Natriumsulfat getrocknet, eingedampft und der Rückstand im Hick mann-Kolben destilliert, wobei man das 5-(a Di- methylaminomethyl-äthyl)-iminodibenzyl vom Kp 0,00s 125-128 erhält. Sein Hydrochlorid schmilzt bei l85,5-187 .
Process for the preparation of a new iyninodibenzyl derivative The present invention relates to a process for the preparation of a new derivative of the iminodibenzyl having valuable pharmacological properties.
It was surprisingly found that the previously unknown 5- (a-dimethylaminomethyl-ethyl) -iminodibenzyl (5- [α-dimethylaminomethyl-ethyl] -10,11-dihydro-5-dibenzo [b, f] azepin) of the formula
EMI0001.0014
capable of considerably increasing the sedative effect of its known isomers and homologues.
It is particularly suitable in combination with the isomeric 5 - (/ 3-dimethylamino-propyl) imnodibenzyl or 5- (y-dimethylamino-propyl) 4iminodibenzyl for the treatment of certain forms of mental illness, especially mental depression, although such combinations are good therapeutic effect and the absence of vegetative side effects.
The inventive method for the preparation of a compound of the formula I is characterized in that an a-halopropionic acid dimethylamide, in particular a-bromopropionic acid dimethyl amide, with iminodibenzyl in the presence of an acid-binding agent or with a Reacts the salt of the iminodibenzyl and the 5- (a-dimethylcarbamylethyl)
-iminodibenzyl with an Alkah.- metal ErdmetaEhydrid ', in particular Uthiumal'umi- niumhyd'rid, reduced.
In the example below, parts mean parts by weight; these relate to parts by volume as g to cms. The temperatures are given in degrees Celsius.
<I> Example </I> 40 parts of iminod'ibenzyl are dissolved in 150 parts by volume of benzene and 50 parts by volume of tolluene.
At 40-50, 40 parts of sodium amide in toluene are added dropwise with stirring and introduction of nitrogen. After the addition of sodium amide, the whole is refluxed for one hour.
Then it is cooled to -15 and 20 parts of a-bromopropionic acid dimethylamide and 20 parts of toluene are added dropwise in such a way that
that the reaction temperature between -10 to 8 can be kept. The reaction mixture is then stirred for a further hour at room temperature and then refluxed for three hours. It is cooled, the separated sodium bromide is filtered off with suction and the filtrate is distilled in a Hickmann flask under high vacuum,
where the 5- (a-dimethylcarbamyl: -äthyi) -imino-dibenzyl is obtained. F: 114-116 (ether).
30 parts of lithium aluminum hydride are abs in 2000 parts by volume. Suspended ether and within 11/2 hours with stirring 240 parts of the ami.des obtained above in 720 parts of tetrahydrofuran were added dropwise, with:
the temperature rises to about <B> 381> </B>. The mixture is then refluxed for three hours, then cooled to -10 and the reaction mixture is decomposed with water.
The ethereal phase is extracted 4-5 times with 200 parts by volume of 2N hydrochloric acid. The sour extracts are made with conc. Sodium hydroxide solution is made alkaline and the oil which has separated out is taken up in ether.
The ethereal solution is dried with sodium sulfate, evaporated and the residue is distilled in a Hickmann flask, giving 5- (a-dimethylaminomethyl-ethyl) -iminodibenzyl with a boiling point of 0.00s 125-128. Its hydrochloride melts at 185.5-187.
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6095558A CH367828A (en) | 1958-06-24 | 1958-06-24 | Process for the preparation of a new iminodibenzyl derivative |
| ES0250295A ES250295A1 (en) | 1958-06-24 | 1959-06-23 | Procedure for the preparation of a new derivative of imiodibencilo (Machine-translation by Google Translate, not legally binding) |
| BE579954A BE579954A (en) | 1958-06-24 | 1959-06-23 | New iminodibenzyl derivative and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH6095558A CH367828A (en) | 1958-06-24 | 1958-06-24 | Process for the preparation of a new iminodibenzyl derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH367828A true CH367828A (en) | 1963-03-15 |
Family
ID=4523305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH6095558A CH367828A (en) | 1958-06-24 | 1958-06-24 | Process for the preparation of a new iminodibenzyl derivative |
Country Status (3)
| Country | Link |
|---|---|
| BE (1) | BE579954A (en) |
| CH (1) | CH367828A (en) |
| ES (1) | ES250295A1 (en) |
-
1958
- 1958-06-24 CH CH6095558A patent/CH367828A/en unknown
-
1959
- 1959-06-23 ES ES0250295A patent/ES250295A1/en not_active Expired
- 1959-06-23 BE BE579954A patent/BE579954A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE579954A (en) | 1959-12-23 |
| ES250295A1 (en) | 1960-01-01 |
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