CH507965A - Verfahren zur Herstellung von Benzodiazepin-Derivaten - Google Patents

Verfahren zur Herstellung von Benzodiazepin-Derivaten

Info

Publication number: CH507965A
Authority: CH; Switzerland
Prior art keywords: formula; compound; phenyl; chloro; oxide
Prior art date: 1966-12-01

Application number

CH1597467A

Other languages

German (de)

English (en)

Inventor

Henryk Sternbach Leo

Metlesics Werner

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.)

1966-12-01

Filing date

1967-11-15

Publication date

1971-05-31

1967-11-15 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1971-05-31 Publication of CH507965A publication Critical patent/CH507965A/de

Links

239000000543 intermediate Substances 0.000 title abstract description 4
229940049706 benzodiazepine Drugs 0.000 title description 5
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 10
229910000474 mercury oxide Inorganic materials 0.000 claims abstract description 4
UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
238000000034 method Methods 0.000 claims description 21
-1 alkali metal phenyl compound Chemical class 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
239000000203 mixture Substances 0.000 claims description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
238000002844 melting Methods 0.000 claims description 12
230000008018 melting Effects 0.000 claims description 12
229910052783 alkali metal Inorganic materials 0.000 claims description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
239000002244 precipitate Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
239000007858 starting material Substances 0.000 claims description 8
230000001419 dependent effect Effects 0.000 claims description 7
239000003960 organic solvent Substances 0.000 claims description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
150000001340 alkali metals Chemical class 0.000 claims description 6
239000012024 dehydrating agents‎ Substances 0.000 claims description 6
JERGQZXGPHHMRW-UHFFFAOYSA-N ClC=1C=CC2=C(C=[N+](CC(N2)=O)[O-])C1 Chemical compound ClC=1C=CC2=C(C=[N+](CC(N2)=O)[O-])C1 JERGQZXGPHHMRW-UHFFFAOYSA-N 0.000 claims description 5
150000001339 alkali metal compounds Chemical class 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
150000001557 benzodiazepines Chemical class 0.000 claims description 5
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 5
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims description 5
GCEREBZETOWKQK-UHFFFAOYSA-N ClC=1C=CC2=C(C=[N+](CC(=N2)NC)[O-])C1 Chemical compound ClC=1C=CC2=C(C=[N+](CC(=N2)NC)[O-])C1 GCEREBZETOWKQK-UHFFFAOYSA-N 0.000 claims description 4
AFLGFOHNVFWWDU-UHFFFAOYSA-N N-[(2-amino-5-chlorophenyl)methylidene]hydroxylamine Chemical compound NC1=C(C=NO)C=C(C=C1)Cl AFLGFOHNVFWWDU-UHFFFAOYSA-N 0.000 claims description 4
239000008346 aqueous phase Substances 0.000 claims description 4
239000007800 oxidant agent Substances 0.000 claims description 4
239000003208 petroleum Substances 0.000 claims description 4
238000001953 recrystallisation Methods 0.000 claims description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 3
229960003529 diazepam Drugs 0.000 claims description 3
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
235000011152 sodium sulphate Nutrition 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
BUCORZSTKDOEKQ-UHFFFAOYSA-N 7-chloro-4-hydroxy-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-imine Chemical compound C=12C=C(Cl)C=CC2=NC(=NC)CN(O)C=1C1=CC=CC=C1 BUCORZSTKDOEKQ-UHFFFAOYSA-N 0.000 claims description 2
YMPXMTJJHMOCFO-UHFFFAOYSA-N 7-chloro-4-hydroxy-n-methyl-5-phenyl-3,5-dihydro-1,4-benzodiazepin-2-amine Chemical compound ON1CC(NC)=NC2=CC=C(Cl)C=C2C1C1=CC=CC=C1 YMPXMTJJHMOCFO-UHFFFAOYSA-N 0.000 claims description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 3
239000012442 inert solvent Substances 0.000 claims 1
YNHGHPCGMBEGEU-UHFFFAOYSA-N 5-phenyl-1h-1,4-benzodiazepine Chemical class C12=CC=CC=C2NC=CN=C1C1=CC=CC=C1 YNHGHPCGMBEGEU-UHFFFAOYSA-N 0.000 abstract description 5
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 abstract description 2
230000015572 biosynthetic process Effects 0.000 abstract description 2
238000003786 synthesis reaction Methods 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
150000001204 N-oxides Chemical class 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
150000002902 organometallic compounds Chemical class 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
XNIUYXYXTHZOIM-UHFFFAOYSA-N [N+]=1(C=CNC=C2C=1C=CC=C2)[O-] Chemical class [N+]=1(C=CNC=C2C=1C=CC=C2)[O-] XNIUYXYXTHZOIM-UHFFFAOYSA-N 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000006297 dehydration reaction Methods 0.000 description 4
239000002904 solvent Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
AOBLJHNWEUOKBW-UHFFFAOYSA-N 6-chloro-2-(chloromethyl)-3-oxidoquinazolin-3-ium Chemical compound ClC=1C=C2C=[N+](C(=NC2=CC1)CCl)[O-] AOBLJHNWEUOKBW-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
239000002253 acid Substances 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000018044 dehydration Effects 0.000 description 3
239000005457 ice water Substances 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 2
HQXZLPBTTLZMBG-UHFFFAOYSA-N 2-chloro-N-[4-chloro-2-(hydroxyiminomethyl)phenyl]acetamide Chemical compound ClCC(=O)NC1=C(C=NO)C=C(C=C1)Cl HQXZLPBTTLZMBG-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
QHOJUCMFGRVAPD-UHFFFAOYSA-N 4-hydroxy-5-phenyl-1,4-benzodiazepine Chemical class C1(=CC=CC=C1)C=1N(C=CN=C2C1C=CC=C2)O QHOJUCMFGRVAPD-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
SLYYPFDRASAEIX-UHFFFAOYSA-N [N+]=1(NC=CC=C2C=1C=CC=C2)[O-] Chemical class [N+]=1(NC=CC=C2C=1C=CC=C2)[O-] SLYYPFDRASAEIX-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000003513 alkali Substances 0.000 description 2
230000002152 alkylating effect Effects 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000012965 benzophenone Substances 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
229960004782 chlordiazepoxide Drugs 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
230000007721 medicinal effect Effects 0.000 description 2
239000000155 melt Substances 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
150000002923 oximes Chemical class 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000011121 sodium hydroxide Nutrition 0.000 description 2
239000000725 suspension Substances 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
XZGPBNBVGKZWKY-UHFFFAOYSA-N 1-hydroxy-1,2-benzodiazepine Chemical compound N1(N=CC=CC2=C1C=CC=C2)O XZGPBNBVGKZWKY-UHFFFAOYSA-N 0.000 description 1
VQZSSIAOLNOHDD-UHFFFAOYSA-N 1-hydroxy-1,4-benzodiazepine Chemical compound ON1C=CN=CC2=CC=CC=C12 VQZSSIAOLNOHDD-UHFFFAOYSA-N 0.000 description 1
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
IVUAAOBNUNMJQC-UHFFFAOYSA-N 5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound C12=CC=CC=C2NC(=O)CN=C1C1=CC=CC=C1 IVUAAOBNUNMJQC-UHFFFAOYSA-N 0.000 description 1
DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
OVLHCKOKHHLOCY-UHFFFAOYSA-N 7-chloro-4-hydroxy-5-phenyl-3,5-dihydro-1H-1,4-benzodiazepin-2-one Chemical compound ClC=1C=CC2=C(C(N(CC(N2)=O)O)C2=CC=CC=C2)C1 OVLHCKOKHHLOCY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
150000008051 alkyl sulfates Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
150000008366 benzophenones Chemical class 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000000378 dietary effect Effects 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000463 material Substances 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
UDAXAATUAUDQCX-UHFFFAOYSA-N n-[(5-chloro-2-nitrophenyl)methylidene]hydroxylamine Chemical compound ON=CC1=CC(Cl)=CC=C1[N+]([O-])=O UDAXAATUAUDQCX-UHFFFAOYSA-N 0.000 description 1
SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical group ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
AKPLHCDWDRPJGD-UHFFFAOYSA-N nordazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 AKPLHCDWDRPJGD-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
230000020477 pH reduction 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
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 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
- C07D243/20—Nitrogen atoms

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CH1597467A 1966-12-01 1967-11-15 Verfahren zur Herstellung von Benzodiazepin-Derivaten CH507965A (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US59820166A	1966-12-01	1966-12-01

Publications (1)

Publication Number	Publication Date
CH507965A true CH507965A (de)	1971-05-31

Family

ID=24394635

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1597467A CH507965A (de)	1966-12-01	1967-11-15	Verfahren zur Herstellung von Benzodiazepin-Derivaten

Country Status (6)

Country	Link
AT (1)	AT277252B (el)
CH (1)	CH507965A (el)
ES (1)	ES347802A1 (el)
GR (1)	GR37780B (el)
NL (1)	NL6716384A (el)
YU (1)	YU34200B (el)

1967
- 1967-11-15 CH CH1597467A patent/CH507965A/de not_active IP Right Cessation
- 1967-11-22 AT AT1053567A patent/AT277252B/de not_active IP Right Cessation
- 1967-11-28 GR GR670137780A patent/GR37780B/el unknown
- 1967-11-30 ES ES347802A patent/ES347802A1/es not_active Expired
- 1967-12-01 NL NL6716384A patent/NL6716384A/xx unknown
- 1967-12-01 YU YU235867A patent/YU34200B/xx unknown

Also Published As

Publication number	Publication date
YU235867A (en)	1978-06-30
ES347802A1 (es)	1969-02-16
AT277252B (de)	1969-12-29
GR37780B (el)	1969-07-14
NL6716384A (el)	1968-06-04
YU34200B (en)	1979-02-28

Legal Events

Date	Code	Title	Description
1982-07-30	PL	Patent ceased

Publication	Publication Date	Title
DE1812205C3 (de)	1978-10-19	Verfahren zur Herstellung von 1-(2-Diäthylaminoäthyl)-5-phenyI-7-chlor-13-dihydro-2H-l,4-benzodiazepin-2-onen und H2-Diäthylaminoäthyl)-2-aminomethyl-S-phenyl-S-chlorindol-Zwischenprodukte
CH510681A (de)	1971-07-31	Neues Verfahren zur Herstellung von 1,4-Benzodiazepinonen und deren Salzen
CH507965A (de)	1971-05-31	Verfahren zur Herstellung von Benzodiazepin-Derivaten
DE1545972A1 (de)	1970-07-02	Verfahren zur Herstellung von Benzodiazepin-Derivaten
DE1955349A1 (de)	1971-01-14	Benzodiazepinderivate und Verfahren zu ihrer Herstellung
DE1965980A1 (de)	1971-01-07	2-(Dioxopiperazino)-benzophenone und Verfahren zu ihrer Herstellung
DE1445073A1 (de)	1968-10-31	Verfahren zur Herstellung von fluorhaltigen Benzodiazepin-Derivaten
CH507966A (de)	1971-05-31	Verfahren zur Herstellung von Benzodiazepinderivaten
DE1770421C3 (de)	1974-05-02	Verfahren zur Herstellung von 1,3-Dihydro-2H-1,4-benzodiazepin-2-onderivaten
DE1817791C3 (de)	1979-12-20	2-Aminomethyl-3-phenylindole und ihre Salze mit Säuren
AT251588B (de)	1967-01-10	Verfahren zur Herstellung von Chinazolin-Derivaten
AT308117B (de)	1973-06-25	Verfahren zur Herstellung von 1-Alkyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepinen bzw. von Salzen hievon
DE1795372C3 (de)	1977-05-26	10.01.68 Japan 1501-68 Verfahren zur Herstellung von 5-(o-Halogenphenyl)-7-halogen-1,3-dihydro-2H-1,4-benzodiazepin-2-onen und 2-Aminomethylindole und ihre Salze
AT292002B (de)	1971-08-10	Verfahren zur Herstellung von Benzodiazepinen bzw. von Salzen derselben
CH530404A (de)	1972-11-15	Verfahren zur Herstellung von Benzodiazepinderivaten
DE2448259A1 (de)	1976-04-22	Verfahren zur herstellung von 2-halogenmethyl-1,4-benzodiazepinen
AT276401B (de)	1969-11-25	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT262295B (de)	1968-06-10	Verfahren zur Herstellung von neuen Benzodiazepin-Derivaten und von deren Säureadditionssalzen
DE2159920A1 (de)	1972-06-29	Verfahren zur Herstellung von substituierten 5-Phenyl-3-H-l,4-benzodiazepinen
DE1695213A1 (de)	1972-01-27	Verfahren zur Herstellung von Benzodiazepin-Derivaten
DE2141904A1 (de)	1972-03-23	Benzodiazepine, Verfahren zu ihrer Herstellung und diese Verbindungen ent haltende Arzneimittel
CH549036A (de)	1974-05-15	Verfahren zur herstellung von neuen benzodiazepin-derivaten.
DE1906254A1 (de)	1969-09-18	Verfahren zur Herstellung von Benzodiazepinen und ihren Salzen
DE1693070A1 (de)	1971-12-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
DE1695143A1 (de)	1970-02-12	Verfahren zur Herstellung von Benzodiazepin-Derivaten