IL22192A - Manufacture of benzodiazepine derivatives - Google Patents

Manufacture of benzodiazepine derivatives

Info

Publication number: IL22192A
Authority: IL; Israel
Prior art keywords: chemical equivalent; alkylate; whenever prepared; obvious chemical; formula
Prior art date: 1963-10-29

Application number

IL22192A

Other languages

English (en)

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.)

1963-10-29

Filing date

1964-10-05

Publication date

1968-01-25

1964-10-05 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1968-01-25 Publication of IL22192A publication Critical patent/IL22192A/en

Links

238000004519 manufacturing process Methods 0.000 title claims description 3
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title claims 8
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title claims 8
238000000034 method Methods 0.000 claims description 24
150000001875 compounds Chemical class 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 11
150000001412 amines Chemical class 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
229940049706 benzodiazepine Drugs 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
229910052783 alkali metal Inorganic materials 0.000 claims description 7
150000001340 alkali metals Chemical class 0.000 claims description 7
BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
229910052751 metal Inorganic materials 0.000 claims description 5
239000002184 metal Substances 0.000 claims description 5
ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 5
230000002378 acidificating effect Effects 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
230000003301 hydrolyzing effect Effects 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
239000003513 alkali Substances 0.000 claims 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
239000000376 reactant Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
239000000203 mixture Substances 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
239000001961 anticonvulsive agent Substances 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
239000003795 chemical substances by application Substances 0.000 description 2
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000003158 myorelaxant agent Substances 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000002904 solvent Substances 0.000 description 2
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
KFDNKXWSTFABQT-UHFFFAOYSA-N 6-chloro-2-(chloromethyl)-3-oxido-4-phenylquinazolin-3-ium Chemical compound [O-][N+]1=C(CCl)N=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 KFDNKXWSTFABQT-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
230000001773 anti-convulsant effect Effects 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 1
239000003874 central nervous system depressant Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
-1 lower alkanols Chemical class 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
125000005394 methallyl group Chemical group 0.000 description 1
239000011707 mineral Substances 0.000 description 1
229940035363 muscle relaxants Drugs 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000007858 starting material 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
- C07D243/20—Nitrogen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- 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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

IL22192A 1963-10-29 1964-10-05 Manufacture of benzodiazepine derivatives IL22192A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US319673A US3312688A (en)	1963-10-29	1963-10-29	Process for preparing 2-aminobenzodiazepines

Publications (1)

Publication Number	Publication Date
IL22192A true IL22192A (en)	1968-01-25

Family

ID=23243220

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL22192A IL22192A (en)	1963-10-29	1964-10-05	Manufacture of benzodiazepine derivatives

Country Status (14)

Country	Link
US (1)	US3312688A (fr)
BE (1)	BE654924A (fr)
BR (1)	BR6463736D0 (fr)
CH (1)	CH443319A (fr)
DE (2)	DE1445910A1 (fr)
DK (1)	DK114271B (fr)
ES (1)	ES305413A1 (fr)
FR (1)	FR1442311A (fr)
GB (1)	GB1058739A (fr)
IL (1)	IL22192A (fr)
NL (3)	NL139527B (fr)
NO (1)	NO118910B (fr)
OA (1)	OA00943A (fr)
SE (2)	SE355580B (fr)

1963
- 1963-10-29 US US319673A patent/US3312688A/en not_active Expired - Lifetime
1964
- 1964-09-30 CH CH1272964A patent/CH443319A/de unknown
- 1964-10-03 DE DE19641445910 patent/DE1445910A1/de active Pending
- 1964-10-03 DE DE19641695217 patent/DE1695217A1/de active Pending
- 1964-10-05 IL IL22192A patent/IL22192A/en unknown
- 1964-10-19 DK DK516164AA patent/DK114271B/da unknown
- 1964-10-22 GB GB43160/64A patent/GB1058739A/en not_active Expired
- 1964-10-26 FR FR992633A patent/FR1442311A/fr not_active Expired
- 1964-10-27 BR BR163736/64A patent/BR6463736D0/pt unknown
- 1964-10-27 NO NO155319A patent/NO118910B/no unknown
- 1964-10-27 NL NL646412484A patent/NL139527B/xx not_active IP Right Cessation
- 1964-10-28 ES ES0305413A patent/ES305413A1/es not_active Expired
- 1964-10-28 BE BE654924D patent/BE654924A/xx unknown
- 1964-10-29 SE SE10586/70A patent/SE355580B/xx unknown
- 1964-10-29 SE SE13019/64A patent/SE329625B/xx unknown
- 1964-12-26 OA OA51038A patent/OA00943A/fr unknown
1971
- 1971-11-15 NL NL7115680A patent/NL7115680A/xx unknown
- 1971-11-15 NL NL7115681A patent/NL7115681A/xx unknown

Also Published As

Publication number	Publication date
DE1445910A1 (de)	1969-01-23
CH443319A (de)	1967-09-15
FR1442311A (fr)	1966-06-17
NL139527B (nl)	1973-08-15
NL7115680A (fr)	1972-02-25
DK114271B (da)	1969-06-16
SE329625B (fr)	1970-10-19
OA00943A (fr)	1968-03-22
NO118910B (fr)	1970-03-02
ES305413A1 (es)	1965-05-01
BR6463736D0 (pt)	1973-07-17
US3312688A (en)	1967-04-04
BE654924A (fr)	1965-04-28
NL6412484A (fr)	1965-05-03
GB1058739A (en)	1967-02-15
DE1695217A1 (de)	1972-02-17
NL7115681A (fr)	1972-02-25
SE355580B (fr)	1973-04-30

Publication	Publication Date	Title
IL28427A (en)	1971-04-28	3,1-Benzaoxazine-2 helices and a process for their preparation
US4150154A (en)	1979-04-17	Amidinoureas
US4469633A (en)	1984-09-04	N-oxides of 5-oxo-1-phenyl-2-benzazepines
IL22192A (en)	1968-01-25	Manufacture of benzodiazepine derivatives
US3754000A (en)	1973-08-21	Derivatives of 3-aminocarbonyl-2-oxazolidinone and their process of preparation
US3462418A (en)	1969-08-19	Preparation of 1,4-benzodiazepin-2-one-4-oxide from 2-lower alkoxy-1,4-benzodiazepine-4-oxide
US3121074A (en)	1964-02-11	Nitro substituted jh-l
US3920687A (en)	1975-11-18	2,3,6,7-tetrahydro-6-phenyl-5h-imidazo(1,2-d)+8 1,4)benzodiazepin-5-ones and diazepines
US4067868A (en)	1978-01-10	Production of quinazolinone compounds
US4247463A (en)	1981-01-27	Process for the preparation of imidazobenzodiazepines
US3686308A (en)	1972-08-22	5-lower alkanoyl-2-glycylamino-benzophenones
FI62072B (fi)	1982-07-30	Foerfarande foer framstaellning av terapeutiskt verkande 7-brom-1-metyl-1-alkoximetyl-5-(2-halogenfenyl)-1h-2,3-dihydro-1,4-benzodiazepiner samt deras syraadditionssalter
CA1047493A (fr)	1979-01-30	Derives de la benzodiazepine
NO132800B (fr)	1975-09-29
DE1493809A1 (de)	1969-02-27	Verfahren zur Herstellung von Benzophenon-Derivaten
Moormann et al.	2004	3-Methyl-4H-[1, 2, 4]-oxadiazol-5-one: a versatile synthon for protecting monosubstituted acetamidines
US3215737A (en)	1965-11-02	Preparation of 2-amino-5-nitro-benzophenone and derivatives thereof
US3850951A (en)	1974-11-26	Triazolobenzodiazepine 5n-oxide derivatives
US3177201A (en)	1965-04-06	Substituted 5-phenyl-3h-1, 4-benzodiazepines and hydrogenation products thereof
US3321520A (en)	1967-05-23	Iminocycloheptatrienes and a process for preparing the same
US3037990A (en)	1962-06-05	Process for preparing 5-phenyl-2-dialkylamino-2-oxazolin-4-ones
HU189631B (en)	1986-07-28	Process for preparing imidazodiazepine derivatives
US4216230A (en)	1980-08-05	Method for alleviating hypertension with amidinoureas
DK156391B (da)	1989-08-14	Analogifremgangsmaade til fremstilling af 3-aminopyrrolderivater
Fan et al.	2005	Preparation of 2‐aminobenzophenones and polysubstituted quinolines through SmI2 promoted reductive cleavage of 3‐aryl‐2, 1‐benzisoxazoles