AT298497B - Verfahren zur Herstellung von neuen Benzodiazepiniumsalzen - Google Patents

Verfahren zur Herstellung von neuen Benzodiazepiniumsalzen

Info

Publication number: AT298497B
Authority: AT; Austria
Prior art keywords: group; benzodiazepinium; acid; dihydro; reaction mixture
Prior art date: 1969-08-28

Application number

AT332771A

Other languages

German (de)

English (en)

Original Assignee

Sankyo Co

Priority date (The priority date 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 date listed.)

1969-08-28

Filing date

1969-10-23

Publication date

1972-05-10

1969-10-23 Application filed by Sankyo Co filed Critical Sankyo Co

1972-05-10 Application granted granted Critical

1972-05-10 Publication of AT298497B publication Critical patent/AT298497B/de

Links

238000000034 method Methods 0.000 title claims description 10
OUQPQNAGQDKWHA-UHFFFAOYSA-N N=1NC=CC=C2C1C=CC=C2 Chemical class N=1NC=CC=C2C1C=CC=C2 OUQPQNAGQDKWHA-UHFFFAOYSA-N 0.000 title claims description 5
238000002360 preparation method Methods 0.000 title claims description 5
239000002253 acid Substances 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 claims description 2
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims 1
150000001298 alcohols Chemical class 0.000 claims 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
150000003254 radicals Chemical class 0.000 claims 1
239000011541 reaction mixture Substances 0.000 description 24
239000000460 chlorine Substances 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
239000002904 solvent Substances 0.000 description 13
239000013078 crystal Substances 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
229910000041 hydrogen chloride Inorganic materials 0.000 description 11
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
-1 N, N -Dimethyl-carbamoyl group Chemical group 0.000 description 9
239000007789 gas Substances 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
238000010992 reflux Methods 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 5
239000000203 mixture Substances 0.000 description 5
WEGOLYBUWCMMMY-UHFFFAOYSA-N 1-bromo-2-propanol Chemical compound CC(O)CBr WEGOLYBUWCMMMY-UHFFFAOYSA-N 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000005187 foaming Methods 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000007858 starting material Substances 0.000 description 3
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
AKPLHCDWDRPJGD-UHFFFAOYSA-N nordazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 AKPLHCDWDRPJGD-UHFFFAOYSA-N 0.000 description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
CGMJQQJSWIRRRL-UHFFFAOYSA-N 7-bromo-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound ClC1=CC=CC=C1C1=NCC(=O)NC2=CC=C(Br)C=C12 CGMJQQJSWIRRRL-UHFFFAOYSA-N 0.000 description 1
ATCCWKYKHCKDGT-UHFFFAOYSA-N 7-bromo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC(Br)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 ATCCWKYKHCKDGT-UHFFFAOYSA-N 0.000 description 1
SQFLYHVKZVYGJE-UHFFFAOYSA-N 7-chloro-1-[(4-chlorophenyl)methyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)CN=C(C=2C=CC=CC=2)C2=CC(Cl)=CC=C21 SQFLYHVKZVYGJE-UHFFFAOYSA-N 0.000 description 1
OQOCCAOXEVYFEH-UHFFFAOYSA-N 7-chloro-1-ethyl-4-(2-hydroxypropyl)-5-phenyl-3,5-dihydro-1H-1,4-benzodiazepin-1-ium-2-one chloride Chemical compound [Cl-].ClC=1C=CC2=C(C(N(CC([NH+]2CC)=O)CC(C)O)C2=CC=CC=C2)C1 OQOCCAOXEVYFEH-UHFFFAOYSA-N 0.000 description 1
PMOYAPWQLZTKJB-UHFFFAOYSA-N 7-chloro-1-ethyl-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 PMOYAPWQLZTKJB-UHFFFAOYSA-N 0.000 description 1
AOOWAUAQVUYDCR-UHFFFAOYSA-N 7-chloro-5-(2-methylphenyl)-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound CC1=CC=CC=C1C1=NCC(=O)NC2=CC=C(Cl)C=C12 AOOWAUAQVUYDCR-UHFFFAOYSA-N 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
RLEYGIFFETWLOM-UHFFFAOYSA-N [Cl-].BrC=1C=CC2=C(C(N(CC([NH2+]2)=O)CCO)C2=CC=CC=C2)C1 Chemical compound [Cl-].BrC=1C=CC2=C(C(N(CC([NH2+]2)=O)CCO)C2=CC=CC=C2)C1 RLEYGIFFETWLOM-UHFFFAOYSA-N 0.000 description 1
SDZAOLLZKXFVIK-UHFFFAOYSA-N [Cl-].ClC=1C=CC2=C(C(N(CC([NH2+]2)=O)CCO)C2=CC=CC=C2)C1 Chemical compound [Cl-].ClC=1C=CC2=C(C(N(CC([NH2+]2)=O)CCO)C2=CC=CC=C2)C1 SDZAOLLZKXFVIK-UHFFFAOYSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
150000001557 benzodiazepines Chemical class 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
CHIFCDOIPRCHCF-UHFFFAOYSA-N delorazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl CHIFCDOIPRCHCF-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002168 ethanoic acid esters Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000013305 food Nutrition 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

AT332771A 1969-08-28 1969-10-23 Verfahren zur Herstellung von neuen Benzodiazepiniumsalzen AT298497B (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP6813469		1969-08-28

Publications (1)

Publication Number	Publication Date
AT298497B true AT298497B (de)	1972-05-10

Family

ID=13364952

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AT332771A AT298497B (de)	1969-08-28	1969-10-23	Verfahren zur Herstellung von neuen Benzodiazepiniumsalzen

Country Status (3)

Country	Link
AT (1)	AT298497B (fr)
CS (1)	CS167267B2 (fr)
RO (1)	RO61211A (fr)

1969
- 1969-10-23 AT AT332771A patent/AT298497B/de not_active IP Right Cessation
- 1969-10-24 CS CS1667469A patent/CS167267B2/cs unknown
- 1969-10-24 RO RO6965569A patent/RO61211A/fr unknown

Also Published As

Publication number	Publication date
CS167267B2 (fr)	1976-04-29
RO61211A (fr)	1978-02-15

Legal Events

Date	Code	Title	Description
1978-06-15	ELJ	Ceased due to non-payment of the annual fee

Publication	Publication Date	Title
AT298497B (de)	1972-05-10	Verfahren zur Herstellung von neuen Benzodiazepiniumsalzen
CH518302A (de)	1972-01-31	Verfahren zur Herstellung von Benzodiazepinderivaten
DE1807642B2 (de)	1977-11-17	Verfahren zur herstellung von dispersions-monoazofarbstoffen
DE2443179B2 (de)	1977-04-28	Verfahren zur herstellung von perchlormethylbenzolen
DE2065714A1 (de)	1975-03-13	Neue benzodiazepinderivate
AT344179B (de)	1978-07-10	Verfahren zur herstellung von neuen benzodiazepinderivaten
DE1695126A1 (de)	1971-04-08	Verfahren zur Herstellung von Areno-oxazinonverbindungen
DE2526380C2 (fr)	1987-12-17
US3492290A (en)	1970-01-27	Process for the preparation of 5-phenyl - 3h - 1,4 - benzodiazepines and novel intermediates
AT302324B (de)	1972-10-10	Verfahren zur Herstellung von neuen Benzodiazepin-Derivaten sowie von Salzen dieser Verbindungen
CH645617A5 (en)	1984-10-15	Trifluoroethylating agent, its preparation and its use for the introduction of a trifluoroethyl group into a nucleophilic compound
DE2834137A1 (de)	1979-02-15	Verfahren zur herstellung von aromatischen nitrilen
CH557827A (de)	1975-01-15	Verfahren zur herstellung von benzodiazepin-derivaten.
CH491937A (de)	1970-06-15	Verfahren zur Herstellung von Benzodiazepin-Derivaten
US3335181A (en)	1967-08-08	Ammonolysis of 2-halo-2'-benzoyl-4'-nitroacetanilides
AT274816B (de)	1969-10-10	Verfahren zur Herstellung von 1,2-Dihydrobenzodiazepinen und von Säureadditionssalzen dieser Verbindungen
DE1954065B2 (de)	1979-01-11	Verfahren zur Herstellung von kondensierten 1,4-Benzodiazepinderivaten
CH566324A5 (en)	1975-09-15	1-Carbamoylalkyl substd. 1,4-benzodiazepin-2-ones prodn - from corresp acids or derivs by reacting with amines, useful as CNS depressants
AT330786B (de)	1976-07-26	Verfahren zur herstellung von neuen diazepinderivaten
AT204547B (de)	1959-07-25	Verfahren zur Herstellung von neuen Oxyketonen
CH602671A5 (en)	1978-07-31	CNS Depressant 5-aryl-benzodiazepine prepn.
AT267531B (de)	1969-01-10	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH505115A (de)	1971-03-31	Verfahren zur Herstellung von Chinazolinderivaten
AT317221B (de)	1974-08-26	Verfahren zur Herstellung von neuen 1,4-Thienodiazepinen und ihren Säureadditionssalzen
AT266144B (de)	1968-11-11	Verfahren zur Herstellung von Benzodiazepin-Derivaten