CH495366A - Verfahren zur Herstellung von Benzodiazepin-Derivaten - Google Patents

Verfahren zur Herstellung von Benzodiazepin-Derivaten

Info

Publication number: CH495366A
Authority: CH; Switzerland
Prior art keywords: oxime; chloro; amino; alkyl; dependent
Prior art date: 1967-08-09

Application number

CH1129667A

Other languages

German (de)

English (en)

Inventor

Joseph Dr Hellerbach

Armin Dr Walser

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.)

1967-08-09

Filing date

1967-08-09

Publication date

1970-08-31

1967-08-09 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1967-08-09 Priority to CH1059070A priority Critical patent/CH506541A/de

1967-08-09 Priority to CH1059170A priority patent/CH500997A/de

1967-08-09 Priority to CH1059270A priority patent/CH503750A/de

1967-08-09 Priority to CH1129667A priority patent/CH495366A/de

1968-06-25 Priority to AT609168A priority patent/AT279621B/de

1968-07-16 Priority to IL30374A priority patent/IL30374A0/xx

1968-07-22 Priority to DE19681770945 priority patent/DE1770945A1/de

1968-08-08 Priority to BE719208D priority patent/BE719208A/xx

1968-08-08 Priority to ES357030A priority patent/ES357030A1/es

1968-08-09 Priority to FR1588550D priority patent/FR1588550A/fr

1968-08-09 Priority to GB3817068A priority patent/GB1198349A/en

1968-08-09 Priority to FR162501A priority patent/FR7753M/fr

1968-08-09 Priority to NL6811366A priority patent/NL6811366A/xx

1968-08-09 Priority to IE976/68A priority patent/IE32263B1/xx

1970-08-31 Publication of CH495366A publication Critical patent/CH495366A/de

Links

229940035363 muscle relaxants Drugs 0.000 title abstract description 3
239000003158 myorelaxant agent Substances 0.000 title abstract description 3
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title abstract 2
229940049706 benzodiazepine Drugs 0.000 title abstract 2
238000000034 method Methods 0.000 claims abstract description 19
-1 benzyloxy, phenyloxy, amino Chemical group 0.000 claims abstract description 17
229910052736 halogen Inorganic materials 0.000 claims abstract description 15
150000002367 halogens Chemical class 0.000 claims abstract description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims abstract description 6
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 3
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
239000007858 starting material Substances 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 3
230000002378 acidificating effect Effects 0.000 claims description 2
150000001350 alkyl halides Chemical class 0.000 claims description 2
239000002168 alkylating agent Substances 0.000 claims description 2
229940100198 alkylating agent Drugs 0.000 claims description 2
230000002152 alkylating effect Effects 0.000 claims description 2
150000008050 dialkyl sulfates Chemical class 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([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 8
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 claims 1
ZGTHEZQZYSLZDD-UHFFFAOYSA-N ClC=1C=CC2=C(C(=[N+](CC(N2)=O)[O-])C2=C(C=CC=C2)F)C1 Chemical compound ClC=1C=CC2=C(C(=[N+](CC(N2)=O)[O-])C2=C(C=CC=C2)F)C1 ZGTHEZQZYSLZDD-UHFFFAOYSA-N 0.000 claims 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 3
125000004423 acyloxy group Chemical group 0.000 abstract description 2
229940125681 anticonvulsant agent Drugs 0.000 abstract description 2
239000001961 anticonvulsive agent Substances 0.000 abstract description 2
229940125723 sedative agent Drugs 0.000 abstract description 2
239000000932 sedative agent Substances 0.000 abstract description 2
125000005208 trialkylammonium group Chemical group 0.000 abstract description 2
125000005210 alkyl ammonium group Chemical group 0.000 abstract 1
230000001773 anti-convulsant effect Effects 0.000 abstract 1
125000005333 aroyloxy group Chemical group 0.000 abstract 1
125000005131 dialkylammonium group Chemical group 0.000 abstract 1
230000000694 effects Effects 0.000 abstract 1
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
239000000243 solution Substances 0.000 description 43
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
239000012071 phase Substances 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
239000000203 mixture Substances 0.000 description 12
150000002923 oximes Chemical class 0.000 description 12
238000003756 stirring Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
239000000155 melt Substances 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
235000002639 sodium chloride Nutrition 0.000 description 8
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 7
239000000047 product Substances 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000012362 glacial acetic acid Substances 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
238000001816 cooling Methods 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000003513 alkali Substances 0.000 description 4
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 4
150000002431 hydrogen Chemical group 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
239000002904 solvent Substances 0.000 description 4
ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
125000004391 aryl sulfonyl group Chemical group 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
239000011347 resin Substances 0.000 description 3
229920005989 resin Polymers 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
KWZYIAJRFJVQDO-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl KWZYIAJRFJVQDO-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
UASDYISPRTUBPU-UHFFFAOYSA-N ClC=1C=C2C(=[N+](C=NC2=CC1)[O-])C1=C(C=CC=C1)Cl Chemical compound ClC=1C=C2C(=[N+](C=NC2=CC1)[O-])C1=C(C=CC=C1)Cl UASDYISPRTUBPU-UHFFFAOYSA-N 0.000 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 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
238000005905 alkynylation reaction Methods 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
235000011089 carbon dioxide Nutrition 0.000 description 2
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
125000005905 mesyloxy group Chemical group 0.000 description 2
KCFSFYOZQBZDLC-UHFFFAOYSA-N methyl 2-bromo-3-chloro-3-oxopropanoate Chemical compound COC(=O)C(Br)C(Cl)=O KCFSFYOZQBZDLC-UHFFFAOYSA-N 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 2
ZTEHQPVGEHUXHI-UHFFFAOYSA-N (2-amino-5-nitrophenyl)-(2-fluorophenyl)methanone Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1F ZTEHQPVGEHUXHI-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
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
XQRYBQMPRPYRKG-UHFFFAOYSA-N 4-(2-fluorophenyl)-6-nitro-3-oxidoquinazolin-3-ium Chemical compound [N+](=O)([O-])C=1C=C2C(=[N+](C=NC2=CC1)[O-])C1=C(C=CC=C1)F XQRYBQMPRPYRKG-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
NGCZVSDAQDYQNS-UHFFFAOYSA-N O=C(C(C(Cl)=O)Br)OCC1=CC=CC=C1 Chemical compound O=C(C(C(Cl)=O)Br)OCC1=CC=CC=C1 NGCZVSDAQDYQNS-UHFFFAOYSA-N 0.000 description 1
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-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 compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
238000007171 acid catalysis Methods 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000002082 anti-convulsion Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
ONACKWARZUZAOL-UHFFFAOYSA-N ethyl 2-bromo-3-chloro-3-oxopropanoate Chemical compound CCOC(=O)C(Br)C(Cl)=O ONACKWARZUZAOL-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 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
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 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
239000007788 liquid Substances 0.000 description 1
AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 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
239000011976 maleic acid Substances 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
125000005394 methallyl group Chemical group 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910017464 nitrogen compound Inorganic materials 0.000 description 1
150000002830 nitrogen compounds Chemical group 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
239000004576 sand Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
239000000080 wetting agent 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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CH1129667A 1967-08-09 1967-08-09 Verfahren zur Herstellung von Benzodiazepin-Derivaten CH495366A (de)

Priority Applications (14)

Application Number	Priority Date	Filing Date	Title
CH1059070A CH506541A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059170A CH500997A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059270A CH503750A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1129667A CH495366A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
AT609168A AT279621B (de)	1967-08-09	1968-06-25	Verfahren zur Herstellung von neuen Nitonen und den Säureadditionssalzen basischer Verbindungen
IL30374A IL30374A0 (en)	1967-08-09	1968-07-16	Benzodiazepine derivatives and process for the manufacture thereof
DE19681770945 DE1770945A1 (de)	1967-08-09	1968-07-22	Verfahren zur Herstellung von Benzodiazepin-Derivaten
BE719208D BE719208A (fr)	1967-08-09	1968-08-08
ES357030A ES357030A1 (es)	1967-08-09	1968-08-08	Procedimiento para la preparacion de derivados de benzodia-cepina.
FR1588550D FR1588550A (fr)	1967-08-09	1968-08-09
GB3817068A GB1198349A (en)	1967-08-09	1968-08-09	Benzdiaz[1,4]Epine Derivatives
FR162501A FR7753M (fr)	1967-08-09	1968-08-09
NL6811366A NL6811366A (fr)	1967-08-09	1968-08-09
IE976/68A IE32263B1 (en)	1967-08-09	1968-08-09	Benzodiazepine derivatives and process for the manufacture thereof

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
CH1059270A CH503750A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1129667A CH495366A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059070A CH506541A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten

Publications (1)

Publication Number	Publication Date
CH495366A true CH495366A (de)	1970-08-31

Family

ID=27176471

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
CH1129667A CH495366A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059270A CH503750A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059070A CH506541A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten

Family Applications After (2)

Application Number	Title	Priority Date	Filing Date
CH1059270A CH503750A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten
CH1059070A CH506541A (de)	1967-08-09	1967-08-09	Verfahren zur Herstellung von Benzodiazepin-Derivaten

Country Status (6)

Country	Link
BE (1)	BE719208A (fr)
CH (3)	CH495366A (fr)
DE (1)	DE1770945A1 (fr)
FR (2)	FR1588550A (fr)
GB (1)	GB1198349A (fr)
NL (1)	NL6811366A (fr)

1967
- 1967-08-09 CH CH1129667A patent/CH495366A/de not_active IP Right Cessation
- 1967-08-09 CH CH1059270A patent/CH503750A/de not_active IP Right Cessation
- 1967-08-09 CH CH1059070A patent/CH506541A/de not_active IP Right Cessation
1968
- 1968-07-22 DE DE19681770945 patent/DE1770945A1/de active Pending
- 1968-08-08 BE BE719208D patent/BE719208A/xx unknown
- 1968-08-09 FR FR1588550D patent/FR1588550A/fr not_active Expired
- 1968-08-09 GB GB3817068A patent/GB1198349A/en not_active Expired
- 1968-08-09 FR FR162501A patent/FR7753M/fr not_active Expired
- 1968-08-09 NL NL6811366A patent/NL6811366A/xx unknown

Also Published As

Publication number	Publication date
NL6811366A (fr)	1969-02-11
DE1770945A1 (de)	1972-01-13
FR7753M (fr)	1970-03-16
BE719208A (fr)	1969-02-10
CH506541A (de)	1971-04-30
FR1588550A (fr)	1970-04-17
CH503750A (de)	1971-02-28
GB1198349A (en)	1970-07-08

Legal Events

Date	Code	Title	Description
1976-03-15	PL	Patent ceased

Publication	Publication Date	Title
DE69725608T2 (de)	2004-07-29	Indolin-2-one derivate, verfahren zu ihrer herstellung und dieseenthaltende arzneimittel
EP0150040B1 (fr)	1994-08-31	Dérivés de imidazobenzodiazépine
US3121076A (en)	1964-02-11	Benzodiazepinones and processes
BG60270B2 (bg)	1994-03-31	Метод за получаване на 5н-2,3-бензодиазепинови производни
DE1810423A1 (de)	1969-10-09	1-Phenyl-4-alkyl-3H-1,4-benzodiazepin-2,5-[1H,4H]-dione und Verfahren zu ihrer Herstellung
DE3700407A1 (de)	1987-07-09	Indolderivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische zubereitungen
EP0387618A1 (fr)	1990-09-19	N-(1,4-benzodiazépin-3-yl)amides 1H-indole-2-carboxyliques 1,7-pontés
CH532065A (de)	1972-12-31	Verfahren zur Herstellung von Benzodiazepinderivaten
US3121074A (en)	1964-02-11	Nitro substituted jh-l
CH495366A (de)	1970-08-31	Verfahren zur Herstellung von Benzodiazepin-Derivaten
US3203990A (en)	1965-08-31	2-amino-2'-halo-5-nitro benzophenones
EP0072029B1 (fr)	1986-10-22	Triazolobenzazépines, procédé et intermédiaires pour leur fabrication et médicaments les contenant
CH500997A (de)	1970-12-31	Verfahren zur Herstellung von Benzodiazepin-Derivaten
US3740413A (en)	1973-06-19	2-benzimidazolecarboxamides
Davis et al.	1964	Anticonvulsants. II. Spiro Compounds. Dibenzo [α, d] cycloheptadiene-5, 5'-hydantoins,-5, 5'-oxazolidinediones, and-5, 2'-succinimides
US3686308A (en)	1972-08-22	5-lower alkanoyl-2-glycylamino-benzophenones
US3329701A (en)	1967-07-04	Cyanobenzophenones
US3853953A (en)	1974-12-10	Alkyl (n-phenylsulfonyloxy) carbamates
DE1695115A1 (de)	1972-03-30	Verfahren zur Herstellung von neuen Furazanderivaten
US3886214A (en)	1975-05-27	Benzodiazepin-2-ones and processes for the preparation thereof
US3772271A (en)	1973-11-13	1-acylamidoalkyl-benzodiazepin-2-ones
US3954838A (en)	1976-05-04	Process for preparing alkyl (n-phenylsulfonyloxy) carbamates
US3435033A (en)	1969-03-25	Indolizinone derivatives
US2841590A (en)	1958-07-01	Indole derivatives
AT309453B (de)	1973-08-27	Verfahren zur Herstellung von neuen Benzodiazepinderivaten und ihren Säureadditionssalzen