AT300817B - Process for the preparation of benzodiazepines - Google Patents
Process for the preparation of benzodiazepinesInfo
- Publication number
- AT300817B AT300817B AT1054670A AT1054670A AT300817B AT 300817 B AT300817 B AT 300817B AT 1054670 A AT1054670 A AT 1054670A AT 1054670 A AT1054670 A AT 1054670A AT 300817 B AT300817 B AT 300817B
- Authority
- AT
- Austria
- Prior art keywords
- benzodiazepines
- general formula
- preparation
- glycylamidobenzophenone
- yield
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 229940049706 benzodiazepine Drugs 0.000 title description 11
- 150000001557 benzodiazepines Chemical class 0.000 title description 8
- 238000002360 preparation method Methods 0.000 title description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000006798 ring closing metathesis reaction Methods 0.000 claims 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- -1 3-amino-4-phenyl-2- (lH ) -quinazolinone Chemical compound 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- HZQDHBGMMKYQDP-UHFFFAOYSA-N n-(2-benzoylphenyl)-2-bromoacetamide Chemical compound BrCC(=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 HZQDHBGMMKYQDP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
<Desc/Clms Page number 1>
Die Erfindung bezieht sich auf ein Verfahren zur Herstellung von Benzodiazepinen der allgemeinen Formel
EMI1.1
in welcher X Wasserstoff, ein Halogen, die Nitrogruppe oder die Trifluormethylgruppe bedeutet.
Benzodiazepine der allgemeinen Formel I sind bekannt und sind ausgesprochen stark wirksame Tranquillisatoren, Muskelrelaxantia, Antikonvulsiva und Hypnotika.
Benzodiazepine der allgemeinen Formel I wurden bisher durch Umsetzung eines Bromacetylaminobenzophenons der allgemeinen Formel
EMI1.2
in welcher X die oben angegebene Bedeutung besitzt, mit Ammoniak hergestellt, womit ein Gemisch des gewünschten Benzodiazepins und eines Glycylamidobenzophenons der allgemeinen Formel
EMI1.3
in welcher X die oben angegebene Bedeutung besitzt, erhalten wurde. Aus dem so erhaltenen Reaktionsgemisch wurde das gewünschte Benzodiazepin abgetrennt, worauf das verbleibende Glycylamidobenzophenon durch Erhitzen ebenfalls in das gewünschte Benzodiazepin übergeführt wurde (vgl. deutsche Auslegeschrift 1136709).
Beim Arbeiten nach dem bekannten Verfahren werden jedoch die gewünschten Benzodiazepine nur mit schlechter Ausbeute erhalten, wozu noch kommt, dass die Aufarbeitung des Reaktionsgemisches sehr schwierig ist, da es beträchtliche Mengen an Nebenprodukten, beispielsweise 3-Amino-4-phenyl-2- (lH)-chinazolinon, enthält.
Es wurde nun gefunden, dass Benzodiazepine der allgemeinen Formel I in hoher Ausbeute und in hoher Reinheit direkt aus Glycylamidobenzophenonen der allgemeinen Formel II erhalten werden können, wenn in Anwesenheit von Dimethylsulfoxyd gearbeitet wird. Dementsprechend ist das erfindungsgemässe Verfahren zur Herstellung von Benzodiazepinen der allgemeinen Formel I dadurch gekennzeichnet, dass ein Glycylamidobenzophenon der allgemeinen Formel
EMI1.4
<Desc/Clms Page number 2>
EMI2.1
EMI2.2
<Desc/Clms Page number 3>
EMI3.1
EMI3.2
liegen also äusserst niedrig.
Demgegenüber wird beim Arbeiten gemäss den obigen Beispielen 1 und 2 im Sinne des Reaktionsschemas
EMI3.3
bei Beispiel 1 eine Ausbeute von 85% und bei Beispiel 2 eine Ausbeute von 93, 5% erzielt. Im Rahmen des erfindungsgemässen Verfahrens ist also die erzielbare Ausbeute beträchtlich höher als beim an sich bekannten Verfahren.
PATENTANSPRÜCHE :
1. Verfahren zur Herstellung von Benzodiazepinen der allgemeinen Formel
EMI3.4
in welcher X Wasserstoff, ein Halogen, die Nitrogruppe oder die Trifluormethylgruppe bedeutet, dadurch gekennzeichnet, dass ein Glycylamidobenzophenon der allgemeinen Formel
EMI3.5
in welcher X die oben angebebene Bedeutung besitzt, in Anwesenheit von Dimethylsulfoxyd cyclisiert wird.
<Desc / Clms Page number 1>
The invention relates to a process for the preparation of benzodiazepines of the general formula
EMI1.1
in which X denotes hydrogen, a halogen, the nitro group or the trifluoromethyl group.
Benzodiazepines of the general formula I are known and are extremely effective tranquillizers, muscle relaxants, anticonvulsants and hypnotics.
Benzodiazepines of the general formula I were previously obtained by reacting a bromoacetylaminobenzophenone of the general formula
EMI1.2
in which X has the meaning given above, prepared with ammonia, whereby a mixture of the desired benzodiazepine and a glycylamidobenzophenone of the general formula
EMI1.3
in which X has the meaning given above, was obtained. The desired benzodiazepine was separated off from the reaction mixture thus obtained, whereupon the remaining glycylamidobenzophenone was likewise converted into the desired benzodiazepine by heating (cf. German Auslegeschrift 1136709).
When working according to the known process, however, the desired benzodiazepines are only obtained with poor yield, and this is compounded by the fact that working up the reaction mixture is very difficult since there are considerable amounts of by-products, for example 3-amino-4-phenyl-2- (lH ) -quinazolinone.
It has now been found that benzodiazepines of the general formula I can be obtained in high yield and in high purity directly from glycylamidobenzophenones of the general formula II if it is carried out in the presence of dimethyl sulfoxide. The process according to the invention for the preparation of benzodiazepines of the general formula I is accordingly characterized in that a glycylamidobenzophenone of the general formula
EMI1.4
<Desc / Clms Page number 2>
EMI2.1
EMI2.2
<Desc / Clms Page number 3>
EMI3.1
EMI3.2
are therefore extremely low.
In contrast, when working according to the above Examples 1 and 2 in the sense of the reaction scheme
EMI3.3
in example 1 a yield of 85% and in example 2 a yield of 93.5% achieved. In the context of the process according to the invention, the yield that can be achieved is considerably higher than in the process known per se.
PATENT CLAIMS:
1. Process for the preparation of benzodiazepines of the general formula
EMI3.4
in which X denotes hydrogen, a halogen, the nitro group or the trifluoromethyl group, characterized in that a glycylamidobenzophenone of the general formula
EMI3.5
in which X has the meaning given above, is cyclized in the presence of dimethyl sulfoxide.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT1054670A AT300817B (en) | 1970-11-23 | 1970-11-23 | Process for the preparation of benzodiazepines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT1054670A AT300817B (en) | 1970-11-23 | 1970-11-23 | Process for the preparation of benzodiazepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT300817B true AT300817B (en) | 1972-08-10 |
Family
ID=3623099
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT1054670A AT300817B (en) | 1970-11-23 | 1970-11-23 | Process for the preparation of benzodiazepines |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT300817B (en) |
-
1970
- 1970-11-23 AT AT1054670A patent/AT300817B/en not_active IP Right Cessation
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AT300817B (en) | Process for the preparation of benzodiazepines | |
| DE1235873B (en) | Process for the production of alkali cyanides | |
| DE1091548B (en) | Process for the continuous production of phosphorus oxychloride | |
| AT299207B (en) | Process for the preparation of new benzodiazepine derivatives and their salts | |
| AT230882B (en) | Process for the production of 6-aminochryses | |
| AT293393B (en) | Process for the preparation of benzodiazepin-2-ones or salts thereof | |
| AT238168B (en) | Process for the preparation of N- (2,3-dimethylphenyl) anthranilic acid and its salts | |
| DE1918311C3 (en) | Process for the preparation of l-carbamoylalkyl-l.S-dihydro ^ H-Mbenzodiazepin-2-one derivatives | |
| AT159191B (en) | Process for the preparation of a chlorocarbon compound of the formula C4Cl6. | |
| AT236373B (en) | Process for the preparation of nicotinic and isonicotinic acid amides | |
| AT215403B (en) | Process for the production of alkali and alkaline earth bromites | |
| AT272305B (en) | Process for the preparation of new 2-aminobenzophenone imines | |
| AT222655B (en) | Process for the preparation of new derivatives of 5H-dibenzo [b, f] azepines or their salts or quaternary ammonium compounds | |
| DE822552C (en) | Process for the preparation of alkyl derivatives of diketooxazolidines | |
| DE869204C (en) | Process for the preparation of diphenylmethane-4, 4'-diacetonitrile | |
| AT314504B (en) | Process for the preparation of N <1> -Benzoylphenyl-ethylenediamine derivatives | |
| AT313900B (en) | Process for the preparation of 2,3-dihydro-1,4-benzodiazepine compounds and their acid addition salts | |
| AT343680B (en) | PROCESS FOR THE PREPARATION OF NEW 1- (N-BUTYL) -3-ALKYL -7- OXOALKYLXANTHINES | |
| AT334379B (en) | PROCESS FOR THE PREPARATION OF NEW 6-AZA-3H-1,4-BENZODIAZEPINES AND THEIR SALTS | |
| AT273968B (en) | Process for the preparation of dihydrokawain or dihydromethysticin | |
| AT343679B (en) | PROCESS FOR THE PRODUCTION OF NEW 1-METHYL-3-ALKYL-7- OXOALKYLXANTHINES | |
| AT270622B (en) | Process for the preparation of new o-hydroxy-p-acylamino-m'-halogenacylophenones | |
| AT275552B (en) | Process for the production of new copper complex salts | |
| AT200580B (en) | Process for the production of low-iron urea | |
| AT216505B (en) | Process for the preparation of pyrazolinobenzimidazoles |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ELJ | Ceased due to non-payment of the annual fee |