NO763172L - PROCEDURES FOR THE PREPARATION OF NEW ORGANIC COMPOUNDS. - Google Patents
PROCEDURES FOR THE PREPARATION OF NEW ORGANIC COMPOUNDS.Info
- Publication number
- NO763172L NO763172L NO763172A NO763172A NO763172L NO 763172 L NO763172 L NO 763172L NO 763172 A NO763172 A NO 763172A NO 763172 A NO763172 A NO 763172A NO 763172 L NO763172 L NO 763172L
- Authority
- NO
- Norway
- Prior art keywords
- carbon atoms
- compounds
- formula
- stands
- organic compounds
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 150000002894 organic compounds Chemical class 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- -1 oxyoxy residue Chemical group 0.000 description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- BLOPFAKSIQBSIG-UHFFFAOYSA-N 11h-benzo[b][1,4]benzodiazepine Chemical compound C1=NC2=CC=CC=C2NC2=CC=CC=C21 BLOPFAKSIQBSIG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/38—[b, e]- or [b, f]-condensed with six-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Electroplating Methods And Accessories (AREA)
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av nye organiske forbindelser med formel I,'-:' The present invention relates to a method for the production of new organic compounds of formula I,'-:'
hvori star for hydrogen, alkyl med 1-4 karbonatomer, hydroksyalkyl med 2 - 4tkarbonatomer eller alkoksyalkyl med tilsammen høyst 5 karbonatomer, R~står for fluor eller klor og R,, står for alkyl med 1-4 karbonatomer, hydroksyalkyi: med 2-4 karbonatomer, alkoksyalkyl•med tilsammen høyst 5 karbonatomer eller alkenyl med 3-4 karbonatomer, med den betingelse at hvis R^betyr metyl, in which stands for hydrogen, alkyl with 1-4 carbon atoms, hydroxyalkyl with 2-4t carbon atoms or alkoxyalkyl with a total of no more than 5 carbon atoms, R~ stands for fluorine or chlorine and R,, stands for alkyl with 1-4 carbon atoms, hydroxyalkyli: with 2- 4 carbon atoms, alkoxyalkyl with a total of no more than 5 carbon atoms or alkenyl with 3-4 carbon atoms, with the proviso that if R^means methyl,
står Rp for fluor,Rp stands for fluorine,
samt syreaddisjonssalter av disse forbindelser.as well as acid addition salts of these compounds.
AL'kyl i R^har foretrukket 1-2 karbonatomer.Al'cyl in R^ has preferred 1-2 carbon atoms.
Aikoksyresten i alkoksyalkyl og hydroksyl i hydroksyalkyl befinner seg foretrukket i endestill ingen av alkylenkjeden og alkylenkjeden har foretrukket 2 eller 3, spesielt 2 karbonatomer. Aikoksyresten i alkoksyalkyl betyr foretrukket medoksy. Dobbeltbindingen i alkenyl befinner seg i 2-3 eller 3-4 stilling. Alkenyl står spesielt for allyl eller 2-metyl-2-propenyl. The oxyoxy residue in alkoxyalkyl and hydroxyl in hydroxyalkyl are preferably located at the end of none of the alkylene chain and the alkylene chain preferably has 2 or 3, especially 2 carbon atoms. The oxyoxy radical in alkoxyalkyl preferably means medoxy. The double bond in alkenyl is in the 2-3 or 3-4 position. Alkenyl stands specifically for allyl or 2-methyl-2-propenyl.
står foretrukket for metyl. R^ betyr foretrukket alkyl eller alkoksyalkyl, spesielt alkyl. Spesielt betyr R^metyl, etyl eller n-propyl., .. preferably stands for methyl. R 1 preferably means alkyl or alkoxyalkyl, especially alkyl. In particular R^ means methyl, ethyl or n-propyl., ..
Det særegne ved fremgangsmåten for fremstilling av de nye forbindelser med formel I og deres syreaddisjonssalter. er at forbindelser med formel II, The peculiarity of the process for the preparation of the new compounds of formula I and their acid addition salts. is that compounds of formula II,
hvori R£og R_ har den ovennevnte betydning, og X betyr en av-spaltbari rest, omsettes med forbindelser med formel III, in which R£ and R_ have the above meaning, and X means a cleavable residue, react with compounds of formula III,
hvori R^har den ovennevnte betydning, og de erholdte forbindelser med formel I overføres eventuelt i sine syreaddisjonssalter. in which R^ has the above-mentioned meaning, and the obtained compounds of formula I are optionally transferred in their acid addition salts.
Fremgangsmåten kan gjennomføres på en for fremstilling av analoge forbindelser kjent måte. The method can be carried out in a manner known for the production of analogue compounds.
I forbindelsen med formel II er X på karbonatomet kovalent eller ionisk bundet og betyr f.eks. aminogruppen, som eventuelt kan være substituert med en eller to alkylgrupper med 1-4 karbonatomer, spesielt metylgruppér, sul f hydr il gruppen, én alkoksy- eller aiLkyl-tiogruppe med 1-5 karbonatomer, f.eks. metoksy- eller metyl-tiogruppen, p-nitrobensyltiogruppen eller tosyloksygruppen eller foretrukket halogen, spesielt klor. In the compound of formula II, X on the carbon atom is covalently or ionically bonded and means e.g. the amino group, which may optionally be substituted with one or two alkyl groups with 1-4 carbon atoms, especially methyl groups, the sulfhydryl group, one alkoxy- or alkyl-thio group with 1-5 carbon atoms, e.g. the methoxy or methylthio group, the p-nitrobenzylthio group or the tosyloxy group or preferably halogen, especially chlorine.
Fremgangsmåten gjennomføres hensiktsmessig ved temperatuner mellom 50 og 170° C i et inert organisk løsningsmiddel, f.eks. xylen eller dioksan. The procedure is suitably carried out at temperatures between 50 and 170° C in an inert organic solvent, e.g. xylene or dioxane.
Forbindelsene med formel I kan isoleres og renses på i og for seg kjent måte. The compounds of formula I can be isolated and purified in a manner known per se.
1 1
Utgangsforbindelsene med formel II kan fremstilles analogt med enThe starting compounds of formula II can be prepared analogously to a
i og for seg k§;ent fremgangsmåte, f.eks. den her beskrevne fremgangsmåte, f.eks. fra det tilsvarende laktam, f.eks. ved omsetning med fosforoksyklorid. in and of itself known method, e.g. the method described here, e.g. from the corresponding lactam, e.g. by reaction with phosphorus oxychloride.
De ved fremgangsmåten i henhold til oppfinnelsen fremstillbare forbindelser med formel I utmerker seg ved farmakodynamiske egen-skaper.'De kan anvendes som neuroleptika. Forbindelser med formel I, hvori R^betyr klor og R^betyr alkyl eller alkenyl, utmerker seg som neuroleptika ved fordelaktige virkninger, f.eks. det vidtgående fravær av bivirkninger i kretsløpet. Forbindelser med formel I hvori R ? står for fluor, har utover dette en anti-depressiv virkning. The compounds of formula I which can be prepared by the method according to the invention are distinguished by their pharmacodynamic properties. They can be used as neuroleptics. Compounds of formula I, in which R₂ is chlorine and R₂ is alkyl or alkenyl, are distinguished as neuroleptics by beneficial effects, e.g. the extensive absence of side effects in the circuit. Compounds of formula I in which R ? stands for fluorine, has an anti-depressant effect.
Forbindelsene med formel I kan også tilføres i form av sine farma-søytiskJtålbare syreaddisjonssalter, f.eks. som hydrokloridet, maleinatet eller fumaratet, som har den samme grad av aktivitet som de fri baser. The compounds of formula I can also be supplied in the form of their pharmaceutically acceptable acid addition salts, e.g. such as the hydrochloride, maleate or fumarate, which have the same degree of activity as the free bases.
Tilførsel av forbindelser med formel I henholdsvis av deres salter kan skje enten oralt i form av tabletter, granulater, kapsler eller drageer, eller parenteralt i form av injeksjonsløsninger. Supply of compounds of formula I or of their salts can take place either orally in the form of tablets, granules, capsules or dragees, or parenterally in the form of injection solutions.
I de etterfølgende eksempler som skal illustrere oppfinnelsen er temperaturene angitt i grader Celsius og er ukorrigert. In the following examples to illustrate the invention, the temperatures are given in degrees Celsius and are uncorrected.
Eksempel 1: 5-n-propyl-8-klor-ll-(4-metyl-l-piperasinyl)-5H-" Example 1: 5-n-propyl-8-chloro-11-(4-methyl-1-piperazinyl)-5H-"
dibenso(b,e)(1,4)diasepindibenzo(b,e)(1,4)diazepine
5,74 g 5-n-propyl-8-klor-10,ll-dihydro-5H-dibenso(b,é)(1,4)diasepin-11-on, 30 ml fosforoksyklorid og 1 ml N,N-dimetylanilin oppvarmes i 3 timer til koking. Den erholdte løsning av imidkloridet av laktamet inndampes til tørrhet i vakuum, resten ettertørkes to ganger 'med xylen og oppvarmes til koking med 20 ml dioksan og 25 ml n-metylpiperasin i 6 timer. Løsningen inndampes deretter i så sterk grad som mulig og resten fordeles mellom ammoniakvann og eter. Eterfasén vaskes to ganger med vann og ekstraheres grundig med fortynnet eddiksyre for fraskilling av de basiske substanser. 5.74 g 5-n-propyl-8-chloro-10,11-dihydro-5H-dibenzo(b,é)(1,4)diazepin-11-one, 30 ml phosphorus oxychloride and 1 ml N,N-dimethylaniline heat for 3 hours until boiling. The obtained solution of the imide chloride of the lactam is evaporated to dryness in vacuo, the residue is dried twice with xylene and heated to boiling with 20 ml of dioxane and 25 ml of n-methylpiperazine for 6 hours. The solution is then evaporated as strongly as possible and the remainder is distributed between ammonia water and ether. The ether phase is washed twice with water and extracted thoroughly with dilute acetic acid to separate the basic substances.
Basen frigis fra de forenede ekstrakter ved tilsetning av natrium- ' hydroksyd, opptas i -kloroform, kloroformfasen vaskes med vann, tørkes over vannfritt natriumsulfat og inndampes til tørrhet. The base is released from the combined extracts by addition of sodium hydroxide, taken up in -chloroform, the chloroform phase is washed with water, dried over anhydrous sodium sulfate and evaporated to dryness.
Resten opptas i eter, filtreres over basisk aluminiumoksyd og om-krystalliseres fra eter/petroleter hvorved man erholder den i overskriften nevnte forbindelse med smeltepunkt 120 - 122° C. The residue is taken up in ether, filtered over basic aluminum oxide and recrystallized from ether/petroleum ether, thereby obtaining the compound mentioned in the title with a melting point of 120 - 122° C.
Utgangsforbindelsen kan fremstilles som følger: 2-nitro-4-klor-difenylamin-2'-karboksylsyre overføres over syre-kloridet i 2-nitro-4-klor-difenylamin-2<1->karboksylsyremetylesteren med smeltepunkt 15.5 - 156° C, denne omsettes med n-propyljodid i nærvær av natriumhydrid i heksametylfosforsyretriamid til n-n-propyl-2-nitro-4-klor-difenylamin-2.1 -karboksylsyremetylester, hvorfra man ved reduksjon med Raney-Nickel i etylasetat erholde n-n-propyl-2-amino-4-klor-difenylamin-2'-karboksylsyremetylesteren, som man underkaster en ringslutning ved flere timers oppvarming -i dioksan i nærvær av natriumamid., hvorved man erholder 8-klor-5-n-propyl-10,ll-dihydro-5H-dibenso(b,e)(1,4)diasepin-ll-on. The starting compound can be prepared as follows: 2-nitro-4-chloro-diphenylamine-2'-carboxylic acid is transferred over the acid chloride in the 2-nitro-4-chloro-diphenylamine-2<1->carboxylic acid methyl ester with melting point 15.5 - 156° C, this is reacted with n-propyl iodide in the presence of sodium hydride in hexamethylphosphoric acid triamide to n-n-propyl-2-nitro-4-chloro-diphenylamine-2.1-carboxylic acid methyl ester, from which, by reduction with Raney-Nickel in ethyl acetate, n-n-propyl-2-amino- The 4-chloro-diphenylamine-2'-carboxylic acid methyl ester, which is subjected to a cyclization by several hours of heating -in dioxane in the presence of sodium amide., thereby obtaining 8-chloro-5-n-propyl-10,11-dihydro-5H- dibenzo(b,e)(1,4)diazepin-ll-one.
Analogt med eksempel 1 og under anvendelse av tilsvarende utgangs-forbindelser, kommer man frem til følgende forbindelse med formel I: Analogous to example 1 and using corresponding starting compounds, the following compound with formula I is arrived at:
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1241475A CH602709A5 (en) | 1975-09-24 | 1975-09-24 | (11)-Piperazinyl dibenzo-(b,e) (1,4)-diazepine derivs. |
| CH1241375A CH599196A5 (en) | 1975-09-24 | 1975-09-24 | (11)-Piperazinyl dibenzo-(b,e) (1,4)-diazepine derivs. |
| CH725076A CH602708A5 (en) | 1976-06-09 | 1976-06-09 | (11)-Piperazinyl dibenzo-(b,e) (1,4)-diazepine derivs. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO763172L true NO763172L (en) | 1977-03-25 |
Family
ID=27175741
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO763172A NO763172L (en) | 1975-09-24 | 1976-09-16 | PROCEDURES FOR THE PREPARATION OF NEW ORGANIC COMPOUNDS. |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5239689A (en) |
| AU (1) | AU1808576A (en) |
| DE (1) | DE2641378A1 (en) |
| DK (1) | DK416476A (en) |
| ES (1) | ES451772A1 (en) |
| FI (1) | FI762646A (en) |
| FR (1) | FR2325381A1 (en) |
| GB (1) | GB1554275A (en) |
| IE (1) | IE43727B1 (en) |
| IL (1) | IL50531A0 (en) |
| NL (1) | NL7610420A (en) |
| NO (1) | NO763172L (en) |
| NZ (1) | NZ182137A (en) |
| PT (1) | PT65629B (en) |
| SE (1) | SE7610219L (en) |
| SU (1) | SU668602A3 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991010661A1 (en) * | 1990-01-11 | 1991-07-25 | Novokuznetsky Nauchno-Issledovatelsky Khimiko-Farmatsevtichesky Institut | DERIVATIVES OF 5-AMINO-8-CHLORINE-DIBENZO[b,e][1,4]-DIAZEPINE AND A PHARMACEUTICAL PREPARATION FOR TREATMENT OF EPILEPSY AND EPILEPTIC STATUS BASED THEREON |
| US6034078A (en) * | 1992-05-29 | 2000-03-07 | Eli Lilly And Company Limited | Thienobenzodiazepine compounds |
| NZ247703A (en) * | 1992-05-29 | 1995-07-26 | Lilly Industries Ltd | Thienobenzdiazepine derivatives and medicaments thereof |
| AU2004308955B2 (en) | 2003-12-22 | 2011-08-04 | Acadia Pharmaceuticals Inc. | Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders |
| WO2013070107A1 (en) * | 2011-11-09 | 2013-05-16 | Общество С Ограниченной Ответственностью "Валентек" | 5h-dibenzo[b,e][1,4]diazepine derivatives and use thereof |
-
1976
- 1976-09-15 DE DE19762641378 patent/DE2641378A1/en not_active Withdrawn
- 1976-09-15 DK DK416476A patent/DK416476A/en unknown
- 1976-09-15 SE SE7610219A patent/SE7610219L/en unknown
- 1976-09-15 FI FI762646A patent/FI762646A/fi not_active Application Discontinuation
- 1976-09-16 NO NO763172A patent/NO763172L/en unknown
- 1976-09-20 NL NL7610420A patent/NL7610420A/en not_active Application Discontinuation
- 1976-09-20 SU SU762402953A patent/SU668602A3/en active
- 1976-09-21 GB GB39054/76A patent/GB1554275A/en not_active Expired
- 1976-09-22 NZ NZ182137A patent/NZ182137A/en unknown
- 1976-09-22 ES ES451772A patent/ES451772A1/en not_active Expired
- 1976-09-22 PT PT65629A patent/PT65629B/en unknown
- 1976-09-22 IL IL50531A patent/IL50531A0/en unknown
- 1976-09-22 IE IE2098/76A patent/IE43727B1/en unknown
- 1976-09-22 JP JP51113199A patent/JPS5239689A/en active Pending
- 1976-09-23 AU AU18085/76A patent/AU1808576A/en not_active Expired
- 1976-09-23 FR FR7628560A patent/FR2325381A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| FR2325381A1 (en) | 1977-04-22 |
| ES451772A1 (en) | 1978-01-01 |
| SU668602A3 (en) | 1979-06-15 |
| GB1554275A (en) | 1979-10-17 |
| DK416476A (en) | 1977-03-25 |
| SE7610219L (en) | 1977-03-25 |
| NL7610420A (en) | 1977-03-28 |
| NZ182137A (en) | 1978-12-18 |
| PT65629A (en) | 1976-10-01 |
| FR2325381B1 (en) | 1978-11-17 |
| IL50531A0 (en) | 1976-11-30 |
| DE2641378A1 (en) | 1977-04-07 |
| IE43727B1 (en) | 1981-05-06 |
| JPS5239689A (en) | 1977-03-28 |
| AU1808576A (en) | 1978-04-06 |
| IE43727L (en) | 1977-03-24 |
| FI762646A (en) | 1977-03-25 |
| PT65629B (en) | 1978-05-10 |
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