CS244409B2 - Method of benzodiazepine derivative production - Google Patents
Method of benzodiazepine derivative production Download PDFInfo
- Publication number
- CS244409B2 CS244409B2 CS806938A CS693880A CS244409B2 CS 244409 B2 CS244409 B2 CS 244409B2 CS 806938 A CS806938 A CS 806938A CS 693880 A CS693880 A CS 693880A CS 244409 B2 CS244409 B2 CS 244409B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- hydrogen
- formula
- amino
- compounds
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 15
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 239000001257 hydrogen Substances 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 150000001412 amines Chemical class 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- -1 nitro, amino Chemical group 0.000 abstract description 23
- 210000003169 central nervous system Anatomy 0.000 abstract description 4
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 abstract 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 2
- 125000004442 acylamino group Chemical group 0.000 abstract 2
- 125000001589 carboacyl group Chemical group 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 abstract 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 10
- 235000019359 magnesium stearate Nutrition 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical compound N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 235000001055 magnesium Nutrition 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000006798 ring closing metathesis reaction Methods 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- PUGDHSSOXPHLPT-UHFFFAOYSA-N 4-fluoro-2-nitroaniline Chemical compound NC1=CC=C(F)C=C1[N+]([O-])=O PUGDHSSOXPHLPT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001409 amidines Chemical class 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- BVPIVWHLXCOLBQ-UHFFFAOYSA-N 3-(2-amino-4-nitroanilino)-1-methylpyrazole-4-carbonitrile Chemical compound CN1C=C(C#N)C(NC=2C(=CC(=CC=2)[N+]([O-])=O)N)=N1 BVPIVWHLXCOLBQ-UHFFFAOYSA-N 0.000 description 2
- FBQOIRKIQMQJNS-UHFFFAOYSA-N 3-amino-1-methylpyrazole-4-carbonitrile Chemical compound CN1C=C(C#N)C(N)=N1 FBQOIRKIQMQJNS-UHFFFAOYSA-N 0.000 description 2
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 description 2
- KCYVMBIUIPNYBO-UHFFFAOYSA-N 6-chloro-2-methyl-1h-pyrazolo[3,4-b][1,5]benzodiazepin-4-amine Chemical compound N1=C(N)C2=CN(C)NC2=NC2=CC=CC(Cl)=C21 KCYVMBIUIPNYBO-UHFFFAOYSA-N 0.000 description 2
- XBWAZCLHZCFCGK-UHFFFAOYSA-N 7-chloro-1-methyl-5-phenyl-3,4-dihydro-2h-1,4-benzodiazepin-1-ium;chloride Chemical compound [Cl-].C12=CC(Cl)=CC=C2[NH+](C)CCN=C1C1=CC=CC=C1 XBWAZCLHZCFCGK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 150000001860 citric acid derivatives Chemical class 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000004533 oil dispersion Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229920001021 polysulfide Polymers 0.000 description 2
- 239000005077 polysulfide Substances 0.000 description 2
- 150000008117 polysulfides Polymers 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical class S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZWTDYJYUPDLEGM-UHFFFAOYSA-N 1,2-benzodiazepine-4-thione Chemical compound S=C1C=NN=C2C=CC=CC2=C1 ZWTDYJYUPDLEGM-UHFFFAOYSA-N 0.000 description 1
- RZKKOBGFCAHLCZ-UHFFFAOYSA-N 1,4-dichloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC=C1Cl RZKKOBGFCAHLCZ-UHFFFAOYSA-N 0.000 description 1
- XNJAYQHWXYJBBD-UHFFFAOYSA-N 1,4-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1F XNJAYQHWXYJBBD-UHFFFAOYSA-N 0.000 description 1
- QDKZHQGXPVFLHU-UHFFFAOYSA-N 1,5-benzodiazepin-2-one Chemical compound O=C1C=CN=C2C=CC=CC2=N1 QDKZHQGXPVFLHU-UHFFFAOYSA-N 0.000 description 1
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- JLAAUZHMAFBKAW-UHFFFAOYSA-N 1-n-(1-methylpyrazol-3-yl)-4-(trifluoromethyl)benzene-1,2-diamine Chemical compound CN1C=CC(NC=2C(=CC(=CC=2)C(F)(F)F)N)=N1 JLAAUZHMAFBKAW-UHFFFAOYSA-N 0.000 description 1
- VMLRGLWEZFXINP-UHFFFAOYSA-N 1h-1,5-benzodiazepin-5-ium;chloride Chemical compound Cl.N1C=CC=NC2=CC=CC=C12 VMLRGLWEZFXINP-UHFFFAOYSA-N 0.000 description 1
- ZAXZHLVISULUAQ-UHFFFAOYSA-N 2-methyl-7-(trifluoromethyl)-1h-pyrazolo[3,4-b][1,5]benzodiazepin-4-amine Chemical compound N1=C(N)C2=CN(C)NC2=NC2=CC=C(C(F)(F)F)C=C21 ZAXZHLVISULUAQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7935846 | 1979-10-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS244409B2 true CS244409B2 (en) | 1986-07-17 |
Family
ID=10508540
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS806938A CS244409B2 (en) | 1979-10-16 | 1980-10-13 | Method of benzodiazepine derivative production |
Country Status (33)
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4404137A (en) * | 1979-10-16 | 1983-09-13 | Lilly Industries Limited | Pyrazolo [3,4-b][1,5]benzodiazepine compounds |
| US4431589A (en) * | 1980-12-11 | 1984-02-14 | Lilly House | Benzodiazepine compounds and their use as pharmaceuticals |
| US4596799A (en) * | 1985-01-29 | 1986-06-24 | Ciba-Geigy Corporation | 9H-pyrrolo[2,1-c]-1,2,4-triazolo[4,3-a][1,4]benzodiazepines |
| TW219896B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1988-07-07 | 1994-02-01 | Duphar Int Res | |
| GB8819059D0 (en) * | 1988-08-11 | 1988-09-14 | Lilly Industries Ltd | Benzodiazepine compounds & their use as pharmaceuticals |
| US5631250A (en) * | 1995-03-24 | 1997-05-20 | Eli Lilly And Company | Process and solvate of 2-methyl-thieno-benzodiazepine |
| US5637584A (en) * | 1995-03-24 | 1997-06-10 | Eli Lilly And Company | Solvate of olanzapine |
| EP1994932A1 (en) * | 2003-01-23 | 2008-11-26 | Arcadia Pharmaceuticals Inc. | Use of N-desmethylclozapine to treat human psychosis |
| US20050085463A1 (en) * | 2003-01-23 | 2005-04-21 | Weiner David M. | Use of N-desmethylclozapine to treat human neuropsychiatric disease |
| US20050250767A1 (en) * | 2003-01-23 | 2005-11-10 | Weiner David M | Use of N-desmethylclozapine to treat human neuropsychiatric disease |
| ES2324713T3 (es) * | 2003-12-22 | 2009-08-13 | Acadia Pharmaceuticals Inc. | Analogos de diaril(a,d)ciclohepteno amino-sustituidos como agonistas muscarinicos y metodos de tratamiento de trastornos neuropsiquiatricos. |
| MXPA06011320A (es) * | 2004-04-01 | 2007-03-21 | Acadia Pharm Inc | Metodo de sintesis y aislamiento de n-desmetilclozapina solida y sus formas cristalinas. |
| WO2007053618A1 (en) * | 2005-10-31 | 2007-05-10 | Acadia Pharmaceuticals Inc. | Prodrugs of muscarinic agonists and methods of treatment of neuropsychiatric disorders |
| JP5438482B2 (ja) * | 2009-12-03 | 2014-03-12 | Ｊｕｋｉ株式会社 | ミシン、ミシンの縫製データ編集装置及びミシンの縫製データ編集プログラム |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3450694A (en) * | 1966-02-23 | 1969-06-17 | Abbott Lab | Substituted benzoxazepines and benzothiazepines |
| US3758479A (en) * | 1967-03-22 | 1973-09-11 | Sandoz Ag | Nitro and sulphamoyl substituted dibenzodiazepines |
| DE1795183B1 (de) * | 1968-08-20 | 1972-07-20 | Thomae Gmbh Dr K | 5,11-Dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-on-derivate und Arzneimittel |
| CA918659A (en) * | 1969-07-31 | 1973-01-09 | Yoshitomi Pharmaceutical Industries | 11-(4-substituted-1-piperazinyl)-dibenzo (b,f) (1,4) thiazepines |
| US4115568A (en) * | 1974-11-26 | 1978-09-19 | Lilly Industries Limited | Thieno[3,2-b]-[1,5]benzodiazepines |
| US4172831A (en) * | 1974-11-26 | 1979-10-30 | Lilly Industries Limited | Thieno-benzodiazepines |
| US3953430A (en) * | 1975-02-24 | 1976-04-27 | American Cyanamid Company | Substituted benzodiazepin-10-ones and method of use |
| US3951981A (en) * | 1975-02-24 | 1976-04-20 | American Cyanamid Company | Substituted benzodiazepines and method of use |
| DE2707270A1 (de) * | 1977-02-19 | 1978-08-24 | Hoechst Ag | Pyrazolo-diazepine und verfahren zu ihrer herstellung |
| DE2707269A1 (de) * | 1977-02-19 | 1978-08-24 | Hoechst Ag | Heterocyclische stickstoffverbindungen und verfahren zu ihrer herstellung |
| US4097597A (en) * | 1977-02-23 | 1978-06-27 | Abbott Laboratories | Dibenzo b,e! 1,4!diazepines |
| IT7851496A0 (it) * | 1977-10-31 | 1978-10-13 | Sandoz Ag | Menti pirazinobenzossazepine loro preparazione e loro impiego quali medica |
| CH643263A5 (de) * | 1979-05-11 | 1984-05-30 | Sandoz Ag | Benzodiazepine, ihre herstellung und verwendung. |
| DE3029281A1 (de) * | 1979-08-03 | 1981-02-19 | Byk Gulden Lomberg Chem Fab | Substituierte tetraazatricyclen, verfahren zu ihrer herstellung, ihre verwendung und sie enthaltende arzneimittel |
| US4404137A (en) * | 1979-10-16 | 1983-09-13 | Lilly Industries Limited | Pyrazolo [3,4-b][1,5]benzodiazepine compounds |
-
1980
- 1980-10-02 US US06/193,200 patent/US4404137A/en not_active Expired - Lifetime
- 1980-10-11 GR GR63138A patent/GR70720B/el unknown
- 1980-10-13 RO RO108967A patent/RO85822B/ro unknown
- 1980-10-13 NZ NZ195248A patent/NZ195248A/xx unknown
- 1980-10-13 CS CS806938A patent/CS244409B2/cs unknown
- 1980-10-13 FR FR8021823A patent/FR2467851A1/fr active Granted
- 1980-10-13 YU YU02615/80A patent/YU261580A/xx unknown
- 1980-10-13 MX MX809093U patent/MX6233E/es unknown
- 1980-10-13 PH PH24717A patent/PH16288A/en unknown
- 1980-10-13 IL IL61264A patent/IL61264A/xx unknown
- 1980-10-13 RO RO102349A patent/RO81351B/ro unknown
- 1980-10-14 AU AU63252/80A patent/AU538500B2/en not_active Ceased
- 1980-10-14 PT PT71913A patent/PT71913B/pt unknown
- 1980-10-14 CA CA000362328A patent/CA1159056A/en not_active Expired
- 1980-10-14 AT AT0510180A patent/AT373889B/de not_active IP Right Cessation
- 1980-10-14 CH CH763980A patent/CH646700A5/fr not_active IP Right Cessation
- 1980-10-14 IT IT49899/80A patent/IT1143047B/it active
- 1980-10-15 FI FI803253A patent/FI67550C/fi not_active IP Right Cessation
- 1980-10-15 EP EP80303649A patent/EP0027390B1/en not_active Expired
- 1980-10-15 DE DE8080303649T patent/DE3068706D1/de not_active Expired
- 1980-10-15 BG BG049366A patent/BG34907A3/xx unknown
- 1980-10-15 ES ES495948A patent/ES8106905A1/es not_active Expired
- 1980-10-15 JP JP14423180A patent/JPS5663987A/ja active Pending
- 1980-10-15 PL PL1980231270A patent/PL135044B1/pl unknown
- 1980-10-15 DK DK437480A patent/DK437480A/da not_active Application Discontinuation
- 1980-10-15 KR KR1019800003960A patent/KR850000471B1/ko not_active Expired
- 1980-10-15 PL PL1980227306A patent/PL126824B1/pl unknown
- 1980-10-15 IE IE2135/80A patent/IE50358B1/en unknown
- 1980-10-15 DD DD80224618A patent/DD153692A5/de unknown
- 1980-10-15 BE BE6/47291A patent/BE885729A/fr not_active IP Right Cessation
- 1980-10-15 LU LU82853A patent/LU82853A1/fr unknown
- 1980-10-15 BG BG057344A patent/BG35042A3/xx unknown
- 1980-10-15 HU HU802502A patent/HU182213B/hu not_active IP Right Cessation
- 1980-10-15 ZA ZA00806342A patent/ZA806342B/xx unknown
- 1980-10-16 AR AR282893A patent/AR228041A1/es active
-
1982
- 1982-07-21 AR AR290034A patent/AR228101A1/es active
- 1982-07-28 PH PH27643A patent/PH17759A/en unknown
- 1982-09-29 US US06/426,580 patent/US4486591A/en not_active Expired - Fee Related
-
1983
- 1983-10-11 GB GB838327127A patent/GB8327127D0/en active Pending
-
1984
- 1984-07-24 KR KR1019840004388A patent/KR850000472B1/ko not_active Expired
- 1984-08-06 US US06/638,181 patent/US4542131A/en not_active Expired - Fee Related
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