CH513186A - Verfahren zur Herstellung von Benzodiazepin-Derivaten - Google Patents

Verfahren zur Herstellung von Benzodiazepin-Derivaten

Info

Publication number: CH513186A
Authority: CH; Switzerland
Prior art keywords: formula; ether; chloro; solution; mol
Prior art date: 1968-06-03

Application number

CH710469A

Other languages

German (de)

English (en)

Inventor

Ian Fryer Rodney

Henryk Sternbach Leo

Original Assignee

Hoffmann La Roche

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.)

1968-06-03

Filing date

1969-05-09

Publication date

1971-09-30

1969-05-09 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1971-09-30 Publication of CH513186A publication Critical patent/CH513186A/de

Links

SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title description 2
229940049706 benzodiazepine Drugs 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 10
125000000217 alkyl group Chemical group 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 15
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical class 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
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 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
230000001419 dependent effect Effects 0.000 claims 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 17
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 abstract description 5
WUZSFIKFFXBHMB-UHFFFAOYSA-N 2-bromo-n-[4-chloro-2-(2-fluorobenzoyl)phenyl]acetamide Chemical compound FC1=CC=CC=C1C(=O)C1=CC(Cl)=CC=C1NC(=O)CBr WUZSFIKFFXBHMB-UHFFFAOYSA-N 0.000 abstract description 2
229940125681 anticonvulsant agent Drugs 0.000 abstract description 2
239000001961 anticonvulsive agent Substances 0.000 abstract description 2
239000003326 hypnotic agent Substances 0.000 abstract description 2
230000000147 hypnotic effect Effects 0.000 abstract description 2
229940035363 muscle relaxants Drugs 0.000 abstract description 2
239000003158 myorelaxant agent Substances 0.000 abstract description 2
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 abstract 1
230000001773 anti-convulsant effect Effects 0.000 abstract 1
239000012267 brine Substances 0.000 abstract 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 abstract 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 abstract 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000002904 solvent Substances 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
-1 lithium aluminum hydride Chemical compound 0.000 description 6
238000010992 reflux Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
239000000203 mixture Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
RHZBRCQIKQUQHQ-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetyl chloride Chemical compound C1=CC=C2C(=O)N(CC(=O)Cl)C(=O)C2=C1 RHZBRCQIKQUQHQ-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
VFYLWKBUEFDTFA-UHFFFAOYSA-N [5-chloro-2-[2-(diethylamino)ethylamino]phenyl]-(2-fluorophenyl)methanol Chemical compound ClC=1C=CC(=C(C(C2=C(C=CC=C2)F)O)C1)NCCN(CC)CC VFYLWKBUEFDTFA-UHFFFAOYSA-N 0.000 description 2
VOXNSVGFHTWQLC-UHFFFAOYSA-N [5-chloro-2-[2-(diethylamino)ethylamino]phenyl]-(2-fluorophenyl)methanone Chemical compound CCN(CC)CCNC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1F VOXNSVGFHTWQLC-UHFFFAOYSA-N 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 2
150000001557 benzodiazepines Chemical class 0.000 description 2
SAADBVWGJQAEFS-UHFFFAOYSA-N flurazepam Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F SAADBVWGJQAEFS-UHFFFAOYSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000007858 starting material Substances 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
DINCAJAWFDEDPU-UHFFFAOYSA-N 7-chloro-1-[2-(ethylamino)ethyl]-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CCNCC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F DINCAJAWFDEDPU-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
PUGVROXLRUQCAF-UHFFFAOYSA-N Flurazepam monohydrochloride Chemical compound Cl.N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F PUGVROXLRUQCAF-UHFFFAOYSA-N 0.000 description 1
VOZNKSGSWYQGBM-UHFFFAOYSA-N N-[4-chloro-2-(2-fluorobenzoyl)phenyl]-2-(diethylamino)acetamide Chemical compound ClC1=CC(=C(NC(CN(CC)CC)=O)C=C1)C(C1=C(C=CC=C1)F)=O VOZNKSGSWYQGBM-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
229910018162 SeO2 Inorganic materials 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000000612 phthaloyl group Chemical class C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000008096 xylene Substances 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
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- 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
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/30—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings
- C07D243/32—Preparation including building-up the benzodiazepine skeleton from compounds already containing hetero rings containing a phthalimide or hydrogenated phthalimide ring system

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CH710469A 1968-06-03 1969-05-09 Verfahren zur Herstellung von Benzodiazepin-Derivaten CH513186A (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US73381768A	1968-06-03	1968-06-03

Publications (1)

Publication Number	Publication Date
CH513186A true CH513186A (de)	1971-09-30

Family

ID=24949221

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH710469A CH513186A (de)	1968-06-03	1969-05-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten

Country Status (8)

Country	Link
AT (1)	AT288406B (da)
CH (1)	CH513186A (da)
DK (1)	DK138044B (da)
ES (1)	ES367957A1 (da)
HU (1)	HU164254B (da)
NL (1)	NL6908397A (da)
SE (2)	SE6907764A0 (da)
YU (1)	YU34203B (da)

1969
- 1969-05-09 CH CH710469A patent/CH513186A/de not_active IP Right Cessation
- 1969-05-26 YU YU130569A patent/YU34203B/xx unknown
- 1969-06-02 SE SE6907764A patent/SE6907764A0/sv unknown
- 1969-06-02 AT AT521369A patent/AT288406B/de not_active IP Right Cessation
- 1969-06-02 ES ES367957A patent/ES367957A1/es not_active Expired
- 1969-06-02 DK DK297369A patent/DK138044B/da not_active IP Right Cessation
- 1969-06-03 NL NL6908397A patent/NL6908397A/xx unknown
- 1969-06-03 HU HUHO001178 patent/HU164254B/hu unknown
1972
- 1972-11-06 SE SE1435972A patent/SE413242B/xx unknown

Also Published As

Publication number	Publication date
DK138044C (da)	1978-11-20
YU34203B (en)	1979-02-28
DK138044B (da)	1978-07-03
ES367957A1 (es)	1971-04-16
AT288406B (de)	1971-03-10
NL6908397A (da)	1969-12-05
HU164254B (da)	1974-01-28
SE6907764A0 (sv)	1969-12-04
SE413242B (sv)	1980-05-12

Legal Events

Date	Code	Title	Description
1986-01-31	PL	Patent ceased

Publication	Publication Date	Title
DE1545934A1 (de)	1970-10-22	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH632511A5 (de)	1982-10-15	Verfahren zur herstellung von diazepinderivaten.
DE2640599C2 (da)	1987-11-05
CH513186A (de)	1971-09-30	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH497436A (de)	1970-10-15	Verfahren zur Herstellung von Benzodiazepin-Derivaten
DE1445913A1 (de)	1969-01-30	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT276400B (de)	1969-11-25	Verfahren zur Herstellung von neuen Benzodiazepin-Derivaten und von deren Säureadditionssalzen und quaternären Salzen
CH502354A (de)	1971-01-31	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT311362B (de)	1973-11-12	Verfahren zur Herstellung von Triazolobenzodiazepin-Derivaten
AT330787B (de)	1976-07-26	Verfahren zur herstellung von neuen diazepinderivaten und deren salzen
AT311365B (de)	1973-11-12	Verfahren zur Herstellung neuer Benzodiazepine bzw. von Säureadditionssalzen hievon
AT308754B (de)	1973-07-25	Verfahren zur Herstellung von Benzodiazepinderivaten und von Säureadditionssalzen hievon
AT378960B (de)	1985-10-25	Verfahren zur herstelllung von neuen imidazo (1,5-a) (1,4)diazepinverbindungen, ihren salzen und optisch aktiven formen
AT252921B (de)	1967-03-10	Verfahren zur Herstellung von neuen Benzodiazepin-Derivaten
AT262294B (de)	1968-06-10	Verfahren zur Herstellung von Benzodiazepin-Derivaten und den entsprechenden 4-Desoxyverbindungen und Salzen
AT309453B (de)	1973-08-27	Verfahren zur Herstellung von neuen Benzodiazepinderivaten und ihren Säureadditionssalzen
AT274816B (de)	1969-10-10	Verfahren zur Herstellung von 1,2-Dihydrobenzodiazepinen und von Säureadditionssalzen dieser Verbindungen
AT395154B (de)	1992-10-12	Verfahren zur herstellung von neuen imidazo(1,5-a)(1,4)diazepinverbindungen
AT256112B (de)	1967-08-10	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT270652B (de)	1969-05-12	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT262295B (de)	1968-06-10	Verfahren zur Herstellung von neuen Benzodiazepin-Derivaten und von deren Säureadditionssalzen
AT275528B (de)	1969-10-27	Verfahren zur Herstellung von neuen 1,4-Benzodiazepinen, ihrer 4-Oxyde sowie Salzen dieser Verbindungen
CH572484A5 (en)	1976-02-13	Substd 4h s-triazolo (43-a)(1 4) benzodiazepins - from 2-(3-halomethy s-triazol-4-yl) benzophenones and ammonia or hexamethylene tetramine
AT273144B (de)	1969-08-11	Verfahren zur Herstellung von neuen Benzoxadiazocin-Derivaten
CH505842A (de)	1971-04-15	Verfahren zur Herstellung von neuen 1,4-Benzodiazepinen bzw. ihren 4-Oxyden