NO163597B - CONTROL DEVICE FOR A ONE OR TWO TRACKED VEHICLE. - Google Patents
CONTROL DEVICE FOR A ONE OR TWO TRACKED VEHICLE. Download PDFInfo
- Publication number
- NO163597B NO163597B NO865183A NO865183A NO163597B NO 163597 B NO163597 B NO 163597B NO 865183 A NO865183 A NO 865183A NO 865183 A NO865183 A NO 865183A NO 163597 B NO163597 B NO 163597B
- Authority
- NO
- Norway
- Prior art keywords
- acid
- chloro
- pyrido
- hexahydro
- benzodiazepine
- Prior art date
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- 150000001204 N-oxides Chemical class 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 239000012442 inert solvent Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 150000004965 peroxy acids Chemical class 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 239000002516 radical scavenger Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- -1 n-amyl Chemical group 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000003610 charcoal Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002026 chloroform extract Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000011976 maleic acid Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 2
- CICNZJJYHQWCLE-UHFFFAOYSA-N 1-[(2-aminophenyl)methyl]piperidine-2-carboxylic acid Chemical class NC1=C(CN2C(CCCC2)C(=O)O)C=CC=C1 CICNZJJYHQWCLE-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- GNHNIRBIZGUCDL-UHFFFAOYSA-N ethyl 1-[(5-chloro-2-nitrophenyl)methyl]piperidine-2-carboxylate Chemical compound CCOC(=O)C1CCCCN1CC1=CC(Cl)=CC=C1[N+]([O-])=O GNHNIRBIZGUCDL-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 1
- YAHSRDAQQHEUPZ-UHFFFAOYSA-N 1-[(2-nitrophenyl)methyl]piperidine-2-carboxylic acid Chemical class OC(=O)C1CCCCN1CC1=CC=CC=C1[N+]([O-])=O YAHSRDAQQHEUPZ-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- CJHKJXZMFZKGHI-UHFFFAOYSA-N 1h-pyrido[2,3-i][1,2]benzodiazepine Chemical compound N1N=CC=CC2=CC=C(N=CC=C3)C3=C12 CJHKJXZMFZKGHI-UHFFFAOYSA-N 0.000 description 1
- OCQAXYHNMWVLRH-UHFFFAOYSA-N 2,3-dibenzoyl-2,3-dihydroxybutanedioic acid Chemical class C=1C=CC=CC=1C(=O)C(O)(C(O)=O)C(O)(C(=O)O)C(=O)C1=CC=CC=C1 OCQAXYHNMWVLRH-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- GLVYLTSKTCWWJR-UHFFFAOYSA-N 2-carbonoperoxoylbenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1C(O)=O GLVYLTSKTCWWJR-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- VERWATQGJOEFMQ-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C=C1CCl VERWATQGJOEFMQ-UHFFFAOYSA-N 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
- 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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 229940091181 aconitic acid Drugs 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- SZIKRGHFZTYTIT-UHFFFAOYSA-N ethyl piperidine-2-carboxylate Chemical compound CCOC(=O)C1CCCCN1 SZIKRGHFZTYTIT-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-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
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- WXKOUJXGDJOJCY-UHFFFAOYSA-N pyrido[2,1-c][1,4]benzodiazepine Chemical compound C1=C2C=CC=CC2=NC=C2C=CC=CN21 WXKOUJXGDJOJCY-UHFFFAOYSA-N 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000012976 tarts Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C17/00—Roller skates; Skate-boards
- A63C17/01—Skateboards
- A63C17/011—Skateboards with steering mechanisms
- A63C17/012—Skateboards with steering mechanisms with a truck, i.e. with steering mechanism comprising an inclined geometrical axis to convert lateral tilting of the board in steering of the wheel axis
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C17/00—Roller skates; Skate-boards
- A63C17/01—Skateboards
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C17/00—Roller skates; Skate-boards
- A63C17/04—Roller skates; Skate-boards with wheels arranged otherwise than in two pairs
- A63C17/045—Roller skis
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C5/00—Skis or snowboards
- A63C5/03—Mono skis; Snowboards
- A63C5/031—Snow-ski boards with two or more runners or skis connected together by a rider-supporting platform
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C5/00—Skis or snowboards
- A63C5/035—Skis or snowboards with ground engaging rolls or belts
-
- A—HUMAN NECESSITIES
- A63—SPORTS; GAMES; AMUSEMENTS
- A63C—SKATES; SKIS; ROLLER SKATES; DESIGN OR LAYOUT OF COURTS, RINKS OR THE LIKE
- A63C2203/00—Special features of skates, skis, roller-skates, snowboards and courts
- A63C2203/46—Skateboards or boards for snow having superimposed decks
Landscapes
- Motorcycle And Bicycle Frame (AREA)
- Vehicle Body Suspensions (AREA)
- Controls For Constant Speed Travelling (AREA)
- Steering Controls (AREA)
Description
Fremgangsmåte for fremstilling av 11-substituerte 8-klor-l,2,3,ll,12,12a-heksahydro (4H, 6H)pyrido/"2 ,1-cJ /JL,4]benzodiazepin-12-oner eller salter eller kvaternæré ammoniumforbindelser eller N-oksyder derav. Process for the preparation of 11-substituted 8-chloro-1,2,3,11,12,12a-hexahydro (4H,6H)pyrido[2,1-cJ/JL,4]benzodiazepine-12-ones or salts or quaternary ammonium compounds or N-oxides thereof.
Nærværende oppfinnelse vedrorer en fremgangsmåte for fremstilling av hittil ukjente 11-substituerte 8-klor-l,2,3,11,12,12a-"heksahydro (4H , 6H) pyrido [ 2,1-c] [l, 4]benzodiazepin-l 2-oner med den generelle formel The present invention relates to a process for the production of hitherto unknown 11-substituted 8-chloro-1,2,3,11,12,12a-"hexahydro (4H,6H)pyrido [2,1-c] [1,4]benzodiazepine -l 2-ones with the general formula
hvor R betyr alkyl, alkenyl eller benzyl, where R means alkyl, alkenyl or benzyl,
eller salter derav med uorganiske eller organiske syrer eller or salts thereof with inorganic or organic acids or
kvaternære ammoniumforbindelser eller N-oksyder derav. quaternary ammonium compounds or N-oxides thereof.
Det har vist seg at disse forbindelser har verdifulle farmakologiske egenskaper. These compounds have been shown to have valuable pharmacological properties.
Uttrykket "alkyl" betyr mettede, monovalente, alifatiske grupper med den generelle formel ~cmH2m+l' ^lvor m er et ^elt tall fra 1 - 10, og omfatter både rette og forgrenete grupper, som f.eks. metyl, etyl, n-propyl, isopropyl, n-butyl, isobutyl, n-amyl, n-heksyl, n-oktyl, isooktyl, nonyl og decyl. Uttrykket "alkenyl" omfatter etylenisk umettede, monovalente, alifatiske grupper med 3-6 karbonatomer, som f.eks. allyl, metallyl og butenyl. The term "alkyl" means saturated, monovalent, aliphatic groups with the general formula ~cmH2m+l' ^lwhere m is a whole number from 1 - 10, and includes both straight and branched groups, such as e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-amyl, n-hexyl, n-octyl, isooctyl, nonyl and decyl. The term "alkenyl" includes ethylenically unsaturated, monovalent, aliphatic groups of 3-6 carbon atoms, such as e.g. allyl, methallyl and butenyl.
Forbindelsene med den generelle formel I fremstilles ifolge oppfinnelsen ved at man omsetter 8-klor-l,2,3,11,12,12a-heksa-hydro(4H,6H)pyrido[2,1-c][l,4jbenzodiazepin-l2-on med formlen The compounds with the general formula I are prepared according to the invention by reacting 8-chloro-1,2,3,11,12,12a-hexa-hydro(4H,6H)pyrido[2,1-c][1,4jbenzodiazepine- l2-on with the formula
med et halogenid eller et sulfat av en alkohol med den generelle formel with a halide or a sulfate of an alcohol of the general formula
hvor R har den ovenfor angitte betydning, where R has the above meaning,
i nærvær av et syrebindende middel og i et inert opplosningsmiddel og, hvis onsket, overforer en forbindelse med den generelle formel I til et syreaddisjonssalt med en uorganisk eller organisk syre eller overforer en forbindelse med den generelle formel I til et kvaternært ammoniumsalt ved behandling med et vanlig kvaterniseringsmiddel eller til et N-oksyd ved behandling av den frie base med hydrogenperoksyd eller med en per-syre. in the presence of an acid-binding agent and in an inert solvent and, if desired, converting a compound of the general formula I into an acid addition salt with an inorganic or organic acid or converting a compound of the general formula I into a quaternary ammonium salt by treatment with a usual quaternizing agent or to an N-oxide by treating the free base with hydrogen peroxide or with a per-acid.
Som syrebindende midler og egnede inerte opplosningsmidler skal nevnes: 1. alkalimetallalkoholater, som natrium- eller kaliummetylat, -etylat, -propylat eller -n- eller -tert. butylat, med natriummetylat eller kalium-tert.butylat som foretrukne midler, og i dimetylsulfoksyd} eller 2. alkalimetallhydrider, som litium-, natrium- eller kalium-hydrid, hvor natriumhydrid er foretrukket i eterlignende opplosningsmidler, som f.eks. i tetrahydrofuran, dioksan og dietylen-glykol-dimetyleter; eller 3. alkalimetallamider, som f.eks. litium-, natrium- eller kaliumamid, hvor natriumamid er foretrukket, i inerte organiske opplosningsmidler, som f.eks. benzen, toluen, xylen$ eller endelig 4. alkyl- eller aryllitium, som f.eks. laverealkyllitium og særlig butyllitium eller fenyllitium, i inerte organiske opplosningsmidler, som f.eks. i benzen, toluen, xylen og heksan. As acid-binding agents and suitable inert solvents, the following should be mentioned: 1. alkali metal alcoholates, such as sodium or potassium methylate, -ethylate, -propylate or -n- or -tert. butylate, with sodium methylate or potassium tert.butylate as preferred agents, and in dimethyl sulfoxide} or 2. alkali metal hydrides, such as lithium, sodium or potassium hydride, where sodium hydride is preferred in ether-like solvents, such as e.g. in tetrahydrofuran, dioxane and diethylene glycol dimethyl ether; or 3. alkali metal amides, such as e.g. lithium, sodium or potassium amide, with sodium amide being preferred, in inert organic solvents, such as e.g. benzene, toluene, xylene$ or finally 4. alkyl or aryllithium, such as e.g. lower alkyllithium and especially butyllithium or phenyllithium, in inert organic solvents, such as e.g. in benzene, toluene, xylene and hexane.
Forbindelser med formel II er kjente fra det franske patent-skrift nr. 1.389.526. Compounds of formula II are known from French patent document No. 1,389,526.
Forbindelsen med formel II fremstilles fra pipecolinsyrealkyl-estere og tilsvarende substituerte o-nitrobenzylhalogenider i inerte opplosningsmidler, som benzen, toluen, xylen, i nærvær av et overskudd av syrebindende middel, som f.eks. kaliumkarbonat, natriumkarbonat. o-nitrobenzyl-pipecolinsyreesterene kan reduseres på i og for seg kjent måte med hydrogen i nærvær av Raney-nikkel ved atmosfæretrykk og romtemperatur, hvorved det oppstår de tilsvarende o-amino-benzyl-pipecolinsyreestere som mellomprodukter. For å unngå en debenzylering ved hyd-reringen må denne straks avbrytes etter opptagelse av den teoretiske mengde hydrogen. De dannede o-aminobenzyl-pipecolinsyreestere kan hydrolyseres og samtidig kondenseres til det onskede pyridobenzodiazepin ved behandling med mineralsyrer, The compound of formula II is prepared from pipecolic acid alkyl esters and correspondingly substituted o-nitrobenzyl halides in inert solvents, such as benzene, toluene, xylene, in the presence of an excess of acid binding agent, such as e.g. potassium carbonate, sodium carbonate. The o-nitrobenzyl-pipecolic acid esters can be reduced in a manner known per se with hydrogen in the presence of Raney nickel at atmospheric pressure and room temperature, whereby the corresponding o-amino-benzyl-pipecolic acid esters arise as intermediate products. In order to avoid debenzylation during the hydrogenation, this must be stopped immediately after absorption of the theoretical amount of hydrogen. The formed o-aminobenzyl-pipecolic acid esters can be hydrolyzed and simultaneously condensed to the desired pyridobenzodiazepine by treatment with mineral acids,
som f.eks. saltsyre, hydrogenbromid, svovelsyre. like for example. hydrochloric acid, hydrogen bromide, sulfuric acid.
De har omhandlede 11-substituerte pyridobenzodiazepiner er racemater, da de har et asymmetrisk karbonatom i 12a-stilling. The 11-substituted pyridobenzodiazepines in question are racemates, as they have an asymmetric carbon atom in the 12a position.
De kan på kjent måte oppspaltes i deres d- og l-former. Men det er også mulig å gå ut fra optisk aktive isomerer med formlen II. Omsetningen ifolge oppfinnelsen kan da gjennomføres uten påvirkning av asymmetri-sentret. They can be split into their d- and l-forms in a known manner. But it is also possible to proceed from optically active isomers with the formula II. The turnover according to the invention can then be carried out without affecting the center of asymmetry.
De 11-substituerte pyridobenzodiazepiner med den generelle formel I kan overfores til deres N-oksyder i 5-stilling. Denne omdannelse kan foretas ved reaksjon mellom de 11-substituerte pyridobenzodiazepiner og hydrogenperoksyd i iseddik eller ved behandling med persyrer, som f.eks. pereddiksyre, perbenzoe-syre, perftalsyre, m-klorperbenzoesyre. De dannede N-oksyder er stereoisomerblandinger bestående av 2 racemater, som på den annen side på kjent måte kan oppspaltes i deres tilsvarende optisk aktive former. The 11-substituted pyridobenzodiazepines of the general formula I can be transferred to their N-oxides in the 5-position. This transformation can be carried out by reaction between the 11-substituted pyridobenzodiazepines and hydrogen peroxide in glacial acetic acid or by treatment with peracids, such as e.g. peracetic acid, perbenzoic acid, perphthalic acid, m-chloroperbenzoic acid. The N-oxides formed are stereoisomer mixtures consisting of 2 racemates, which, on the other hand, can be cleaved in a known manner into their corresponding optically active forms.
Nærværende oppfinnelse omfatter som nevnt også fremstillingen As mentioned, the present invention also includes the preparation
av farmasoytisk aksepterbare, ikke-toksiske syreaddisjonssalter som kan fremstilles på i og for seg kjent måte under anvendelse av egnede uorganiske eller organiske syrer, som f.eks. saltsyre, hydrogenbromid, svovelsyre, fosforsyre, eddiksyre, melkesyre, ravsyre, maleinsyre, aconitsyre ftalsyre, vinsyre. of pharmaceutically acceptable, non-toxic acid addition salts which can be prepared in a manner known per se using suitable inorganic or organic acids, such as e.g. hydrochloric acid, hydrogen bromide, sulfuric acid, phosphoric acid, acetic acid, lactic acid, succinic acid, maleic acid, aconitic acid, phthalic acid, tartaric acid.
De kvaternære ammoniumsalter av forbindelser med den generelle formel I fås ved addisjon av alkyl- eller aralkylestere av uorganiske syrer eller organiske sulfonsyrer, som f.eks. metyl-klorid, metylbromid, metyljodid, etylbromid, propylbromid, benzylklorid, benzylbromid, metylsulfat, metylbenzoesulfonat og metyl-p-toluensulfonat, til de tilsvarende frie baser. The quaternary ammonium salts of compounds with the general formula I are obtained by addition of alkyl or aralkyl esters of inorganic acids or organic sulphonic acids, such as e.g. methyl chloride, methyl bromide, methyl iodide, ethyl bromide, propyl bromide, benzyl chloride, benzyl bromide, methyl sulfate, methyl benzoesulfonate and methyl p-toluenesulfonate, to the corresponding free bases.
Som allerede nevnt, har de omhandlende forbindelser med den generelle formel I verdifulle farmakologiske egenskaper. Særlig oppviser de analgetisk, beroligende eller lokalanestetisk virk-ning eller flere av disse virkninger, hvilket kan påvises ved vanlige farmakologiske proveforsok. De ved fremgangsmåten As already mentioned, the compounds of the general formula I in question have valuable pharmacological properties. In particular, they exhibit an analgesic, sedative or local anesthetic effect or several of these effects, which can be demonstrated by normal pharmacological tests. They know the procedure
ifolge oppfinnelsen fremstilte forbindelser kan anvendes oralt eller parenteralt i vanlige doseringsformer, som f.eks. tablet-ter, kapsler eller injeksjonsopplosninger, etter vanlig farma-søytisk administrasjonspraksis. compounds produced according to the invention can be used orally or parenterally in usual dosage forms, such as e.g. tablets, capsules or injection solutions, according to usual pharmaceutical administration practice.
De nedenstående eksempler belyser fremgangsmåten ifolge oppfinnelsen nærmere, idet der i nedenstående eksempler anvendes folgende nomenklatur: The examples below illustrate the method according to the invention in more detail, as the following nomenclature is used in the examples below:
1,2,3,11,12,12a-heksahydro(4H,6H)pyri do[2,1-c][l,4]benzodiazepin-12(llH)-on. 1,2,3,11,12,12a-Hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12(11H)-one.
Temperaturene er angitt i Celsiusgrader. The temperatures are indicated in degrees Celsius.
EKSEMPEL 1. EXAMPLE 1.
8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c] 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c]
[ l, 4] benzodiazepin- l2- on [l,4]benzodiazepine-l2-one
Man suspenderer 6,27 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H) pyrido[2,1-cJ[l,4]benzodiazepin-l2-on (smp. 224 - 225°) i 50 ml absolutt dimetylsulfoksyd, tilsetter 1,5 g natriummetylat og rorer ved romtemperatur i 30 minutter. Derpå tilsettes 5,3 g metyljodid på en gang til denne opplosning, og det rores videre 1 time. Reaksjonsopplosningen helles derpå under omroring i 6.27 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-cJ[1,4]benzodiazepine-12-one (m.p. 224 - 225°) in 50 ml of absolute dimethyl sulfoxide, add 1.5 g of sodium methylate and stir at room temperature for 30 minutes. 5.3 g of methyl iodide are then added all at once to this solution, and stirring is continued for 1 hour. The reaction solution is then poured under stirring
500 ml koldt vann. Reaksjonsblandingen gjores alkalisk ved tilsetning av 2-n natriumhydroksydopplosning og står til henstand i kjoleskap i 16 timer. Det utfelles et krystallinsk bunnfall, som filtreres fra, torkes og omkrystalliseres fra heksan, smp. 107 - 108°. 500 ml cold water. The reaction mixture is made alkaline by the addition of 2-n sodium hydroxide solution and allowed to stand in a refrigerator for 16 hours. A crystalline precipitate is precipitated, which is filtered off, dried and recrystallized from hexane, m.p. 107 - 108°.
Dette 'stoff kan fremstilles på folgende måte: This substance can be produced in the following way:
a) Man rbrer 10 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H) pyrido[2,1-c][l,4]benzodiazepin-l2-on og 4,5 g tert. kaliumbutylat i 80 ml absolutt dimetylsulfoksyd til det oppstår en klar opplosning. Deretter tilsetter man på en gang 2,5 g dimetyl-sulfat og rorer opplosningen i 20 timer. Reaksjonsopplosningen helles så på isvann og den utfelte, gummilignende masse trekkes ut med kloroform. Det organiske uttrekk vaskes med vann, torkes over natriumsulfat, filtreres og inndampes endelig under forminsket trykk. Den til dels faste rest opptas i kokende heksan, og heksanopplosningen inndampes til et lite volum. Det krystal-liserte 8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-l2-on filtreres fra og omkrystalliseres fra heksan. Smeltepunkt 107 - 108°. b) 50 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido[2,1-c] a) 10 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one and 4,5 g tart. of potassium butylate in 80 ml of absolute dimethylsulfoxide until a clear solution occurs. 2.5 g of dimethylsulphate is then added all at once and the solution is stirred for 20 hours. The reaction solution is then poured onto ice water and the precipitated, rubber-like mass is extracted with chloroform. The organic extract is washed with water, dried over sodium sulphate, filtered and finally evaporated under reduced pressure. The partially solid residue is taken up in boiling hexane, and the hexane solution is evaporated to a small volume. The crystallized 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one is filtered from and recrystallized from hexane. Melting point 107 - 108°. b) 50 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c]
[l,4]benzodiazepin og 22,4 g tert. kaliumbutylat rbres sammen i [1,4]benzodiazepine and 22.4 g of tert. potassium butylate is mixed in
250 ml absolutt dimetylsulfoksyd, inntil en klar opplosning oppstår. Deretter tilsetter man 31 g metyljodid dertil og rorer opplosningen i 20 timer. Reaksjonsblandingen helles derpå 250 ml of absolute dimethylsulfoxide, until a clear solution occurs. 31 g of methyl iodide is then added thereto and the solution is stirred for 20 hours. The reaction mixture is then poured
i isvann, og den utfelte gummilignende masse ekstraheres med kloroform. Det organiske ekstrakt vaskes med vann, torkes over natriumsulfat, filtreres og konsentreres under forminsket trykk. Resten opptas i kokende heksan. Heksanopplosningen fordampes til torrhet, og resten omkrystalliseres fra heksan. Smeltepunkt 107 - 108°. in ice water, and the precipitated gum-like mass is extracted with chloroform. The organic extract is washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue is taken up in boiling hexane. The hexane solution is evaporated to dryness, and the residue is recrystallized from hexane. Melting point 107 - 108°.
Det ovenfor som utgangsmateriale anvendte 8-klor-l,2,3,11,12, 12a-heksahydro(4H,6H)pyrido[2,1-c][l,4]benzodiazepin-l2-on kan fremstilles som folger: a) N-(2-nitro-5-klor-benzyl)-pipecolinsyre-etylester 33,3 g pipecolinsyre-etylester opploses i 200 ml vannfritt toluen, som tilsettes 34 g kaliumkarbonat, og dertil dryppes under omroring en opplosning av 44,54 g 2-nitro-5-klor-benzylklorid i 300 ml vannfritt toluen. Etter avsluttet tilsetning kokes blandingen i 12 timer med tilbakelopskjoling. Etter avkjoling gjores den sur, og reaksjonsblandingen ekstraheres uttommende med 3-n saltsyre. De forente sure uttrekk vaskes The 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one used above as starting material can be prepared as follows: a) N-(2-nitro-5-chloro-benzyl)-pipecolic acid ethyl ester 33.3 g of pipecolic acid ethyl ester are dissolved in 200 ml of anhydrous toluene, to which are added 34 g of potassium carbonate, and to this is added dropwise while stirring a solution of 44.54 g of 2-nitro-5-chloro-benzyl chloride in 300 ml of anhydrous toluene. After the addition is complete, the mixture is boiled for 12 hours with reflux. After cooling, it is made acidic, and the reaction mixture is extracted to exhaustion with 3-n hydrochloric acid. The combined acidic extracts are washed
med etylacetat og gjores derpå sterkt basiske. Den utskilte olje ekstraheres med eter; eteruttrekket vaskes med vann, torkes over natriumsulfat, og opplosningsmidlet fjernes under forminsket trykk. Ved vakuumdestillasjon av resten fås det onskede produkt i form av en gul viskos olje med kp. 153 - 154°. b) N-( 2- amino- 5- klor- benzyl)- pipecolinsyre- etylester 7,5 g N-(2-nitro-5-klor-benzyl)-pipecolinsyre-etylester opploses i 100 ml etanol og hydreres ved romtemperatur og atmosfæretrykk over Raney-nikkel. Det opptas 1670 ml hydrogen. Katalysatoren fjernes ved filtrering, og filtratet inndampes til torrhet under forminsket trykk. Ved destillasjon av resten fås det onskede mellomprodukt i form av en olje med kp. 154° ved 0,3 mm Hg-trykk. c) 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido[2,1-c] with ethyl acetate and then made strongly basic. The separated oil is extracted with ether; the ether extract is washed with water, dried over sodium sulfate, and the solvent is removed under reduced pressure. By vacuum distillation of the residue, the desired product is obtained in the form of a yellow viscous oil with bp. 153 - 154°. b) N-(2-amino-5-chloro-benzyl)-pipecolic acid ethyl ester 7.5 g of N-(2-nitro-5-chloro-benzyl)-pipecolic acid ethyl ester are dissolved in 100 ml of ethanol and hydrated at room temperature and atmospheric pressure over Raney nickel. 1670 ml of hydrogen is taken up. The catalyst is removed by filtration, and the filtrate is evaporated to dryness under reduced pressure. By distillation of the residue, the desired intermediate product is obtained in the form of an oil with bp. 154° at 0.3 mm Hg pressure. c) 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c]
[ l, 4] benzodiazepin- l2- on [l,4]benzodiazepine-l2-one
20,0 g N-(2-amino-5-klor-benzyl)-pipecolinsyre-etylester og 350 ml 3-n saltsyre kokes i 5 timer med tilbakelopskjoling. Etter avkjoling innstilles opplosningen på en pH-verdi på 10 og ekstraheres uttommende med kloroform. De forente kloroform-uttrekk vaskes med vann, torkes over natriumsulfat, og opplosningsmidlet fjernes i vakuum. Tilbake blir en hvit krystallinsk rest, som omkrystalliseres fra etanol. Produktet smelter ved 224 - 225°. 20.0 g of N-(2-amino-5-chloro-benzyl)-pipecolic acid ethyl ester and 350 ml of 3-n hydrochloric acid are boiled for 5 hours under reflux. After cooling, the solution is adjusted to a pH value of 10 and extracted exhaustively with chloroform. The combined chloroform extracts are washed with water, dried over sodium sulfate, and the solvent is removed in vacuo. A white crystalline residue remains, which is recrystallized from ethanol. The product melts at 224 - 225°.
EKSEMPEL 2 EXAMPLE 2
8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido[2,1-c] 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c]
[ l, 4] benzodiazepin- l2- on- 5- oksyd [1,4]benzodiazepine-12-one-5-oxide
Man opploser 5 g 8-klor-ll-metyl-l,2,3,11-12,12a-heksahydro (4H,6H)pyrido[2,1-c][l,4]benzodiazepin-l2-on og 9 g m-klorperbenzoesyre i 50 ml kloroform og koker i 4 timer under tilbake-lop. Deretter avkjoles og reaksjonsopplosningen vaskes forst med mettet natriumkarbonatopplosning, deretter med vann. Man inndamper og omkrystalliserer resten 2 ganger fra aceton, hvorved man behandler den med dyrekull. Man oppnår N-oksydet som hvite krystaller med smeltepunkt 197 - 198° (spaltning). 5 g of 8-chloro-11-methyl-1,2,3,11-12,12a-hexahydro (4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one and 9 g of m-chloroperbenzoic acid in 50 ml of chloroform and boil for 4 hours under reflux. It is then cooled and the reaction solution is washed first with saturated sodium carbonate solution, then with water. The residue is evaporated and recrystallized twice from acetone, whereby it is treated with animal charcoal. The N-oxide is obtained as white crystals with a melting point of 197 - 198° (decomposition).
Fra moderlutene kan det andre isomer isoleres. From the mother liquors the second isomer can be isolated.
EKSEMPEL 3 EXAMPLE 3
8-klor-5,11-dimetyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-l2-on-jodid 5 g 8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-l2-on opploses ved romtemperatur i 25 ml metyljodid. Etter 15 timer fordampes metyljodidet under forminsket trykk, og resten vaskes med aceton. 8-chloro-5,11-dimethyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one-iodide 5 g 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one is dissolved at room temperature in 25 ml methyl iodide. After 15 hours, the methyl iodide is evaporated under reduced pressure, and the residue is washed with acetone.
Produktet, en hvit krystallin substans, omkrystalliseres fra vann under tilsetning av dyrekull. Smeltepunkt 283 - 284° The product, a white crystalline substance, is recrystallized from water with the addition of animal charcoal. Melting point 283 - 284°
(spaltning). (fission).
EKSEMPEL 4 EXAMPLE 4
(+) 8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [ 2, 1- c][ l, 4] benzodiazepin- l2- on (+) 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one
Man opploser 16,1 g racemiskt 8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido[2,1-c][l,4]benzodiazepin-l2-on og 22,9 g dibenzoyl-l-vinsyre i 700 ml varm isopropanol. Deretter tilsetter man forsiktig vann, inntil opplosningen begynner å bli blakk og lar blandingen stå 2 dager ved 5°. Det utfelles et salt, hvilket filtreres fra. Man suspenderer saltet i etanol for fjerning av litt oljelignende materiale, filtrerer ennå en gang og omkrystalliserer fra isopropanol. Man oppnår således produktet med smeltepunkt 154 - 155° (spaltning); [<x]p = +292 , (c = 1,665 i dimetylsulfoksyd; 10 cm). 16.1 g of racemic 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12- on and 22.9 g of dibenzoyl-l-tartaric acid in 700 ml of hot isopropanol. Water is then carefully added until the solution starts to become cloudy and the mixture is allowed to stand for 2 days at 5°. A salt is precipitated, which is filtered off. The salt is suspended in ethanol to remove some oil-like material, filtered once more and recrystallized from isopropanol. One thus obtains the product with a melting point of 154 - 155° (cleavage); [<x]p = +292 , (c = 1.665 in dimethyl sulfoxide; 10 cm).
Man spalter dette salt (5 g) med l-n natronlut og ekstraherer den frie base med kloroform. Kloroformekstraktet torkes over natriumsulfat, filtreres og konsentreres under forminsket trykk. Den tilbakeblivende olje krystalliseres fra heksan og omkrystalliseres. Smeltepunkt 109 - 110°; [a]^7 = +385° (c = 1,8 i etanol; 10 cm). This salt (5 g) is split with 1-1 sodium hydroxide solution and the free base is extracted with chloroform. The chloroform extract is dried over sodium sulphate, filtered and concentrated under reduced pressure. The remaining oil is crystallized from hexane and recrystallized. Melting point 109 - 110°; [a]^7 = +385° (c = 1.8 in ethanol; 10 cm).
EKSEMPEL 5 EXAMPLE 5
(-) 8-klor-ll-metyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-12-on (-) 8-chloro-11-methyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one
Man anvender 24,9 g racemiskt 8-klor-l,2,3,11,12,12a-heksa-hydro(4H,6H)pyrido[2,1-c][l,4]benzodiazepin-l2-on ved hjelp av 33,5 g dibenzoyl-d-vinsyre ([cc]D 2 4^ = -69,8 o c = 1,81 i etanol; 10 cm) i 150 ml absolutt etanol til dibenzoylvinsyre-salt. Etanolen fjernes deretter, og resten opploses i en kokende etanol-vann blanding (bestående av ca. 1000 ml vann og 500 ml etanol). Ved henstand utfelles et delvis krystallint bunnfall. Den overskytende opplosning avdekanteres, og den gummilignende rest vaskes med varm etanol og filtreres. Det således erholdte salt omkrystalliseres fra isopropanol, smp. 181 - 182°;[cc]p<5>° = -225° (c = 1,185 i dimetylsulfoksyd; 24.9 g of racemic 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one are used at using 33.5 g of dibenzoyl-d-tartaric acid ([cc]D 2 4^ = -69.8 o c = 1.81 in ethanol; 10 cm) in 150 ml of absolute ethanol to dibenzoyltartaric acid salt. The ethanol is then removed, and the residue is dissolved in a boiling ethanol-water mixture (consisting of approx. 1000 ml of water and 500 ml of ethanol). On standing, a partially crystalline precipitate precipitates. The excess solution is decanted off, and the gum-like residue is washed with hot ethanol and filtered. The salt thus obtained is recrystallized from isopropanol, m.p. 181 - 182°; [cc]p<5>° = -225° (c = 1.185 in dimethylsulfoxide;
10 cm). Dette salt spaltes med l-n natronlut og ekstraheres 10 cm). This salt is split with l-n sodium hydroxide solution and extracted
med kloroform. Kloroformuttrekket torkes over natriumsulfat og konsentreres under forminsket trykk. Den tilbakeblivende olje krystalliseres fra heksan og omkrystalliseres. Man oppnår det rene produkt med smeltepunkt 110 - 111 o ; [ajj2j 5^ = with chloroform. The chloroform extract is dried over sodium sulfate and concentrated under reduced pressure. The remaining oil is crystallized from hexane and recrystallized. The pure product with a melting point of 110 - 111 o is obtained; [ajj2j 5^ =
-368° (c = 2,16 i etanol; 10 cm). -368° (c = 2.16 in ethanol; 10 cm).
EKSEMPEL 6 EXAMPLE 6
8-klor-ll-etyl-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-l2-on 8-chloro-11-ethyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one
Man tilsetter 25,1 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H) pyrido[2,lc][l,4]benzodiazepin-l2-on og 5,4 g natriummetylat til 500 ml absolutt dimetylsulfoksyd og rorer blandingen i 30 minutter ved 50°. Til den således erholdte opplosning tilsetter man langsomt ved den samme temperatur 15,6 g etyl-jodid og oppvarmer reaksjonsopplosningen ytterligere i 5 timer. Den avkjolte reaksjonsblanding helles deretter i ca. 1000 ml isvann, og blandingen innstilles alkalisk med kaliumkarbonat. Det vandige skikt avdekanteres så fra det gummilignende bunnfall. Bunnfallet opploses i kloroform, kloroformopplosningen vaskes med vann, behandles med dyrekull, filtreres og konsentreres under forminsket trykk. Den således erholdte olje destilleres i hoyvakuum, kp. 152 - 154°/0,015 mm Hg-trykk. Den 25.1 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,lc][1,4]benzodiazepine-12-one and 5.4 g of sodium methylate are added to 500 ml of absolute dimethyl sulfoxide and stir the mixture for 30 minutes at 50°. To the solution thus obtained, 15.6 g of ethyl iodide are added slowly at the same temperature and the reaction solution is further heated for 5 hours. The cooled reaction mixture is then poured into approx. 1000 ml of ice water, and the mixture is made alkaline with potassium carbonate. The aqueous layer is then decanted from the rubber-like precipitate. The precipitate is dissolved in chloroform, the chloroform solution is washed with water, treated with animal charcoal, filtered and concentrated under reduced pressure. The oil thus obtained is distilled in high vacuum, bp. 152 - 154°/0.015 mm Hg pressure. It
gule olje krystalliseres fra heksan og omkrystalliseres fra yellow oil is crystallized from hexane and recrystallized from
det samme opplosningsmiddel, smeltepunkt 58 - 59°. the same solvent, melting point 58 - 59°.
EKSEMPEL. 7 EXAMPLE. 7
ll-allyl-8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [ 2, 1- c][ l, 4] benzodiazepin- l2- on- hydroklorid 11-allyl-8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one hydrochloride
Man opploser 5,0 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H) pyrido[2,1-c][l,4]benzodiazepin-l2-on og 1,2 g natriummetylat i 60 ml absolutt dimetylsulfoksyd og rorer blandingen i 18 timer. Reaksjonsopplosningen helles deretter i 500 ml iskaldt vann, og det utfelte produkt ekstraheres med eddikester. Den organiske opplosning behandles med 2-n saltsyre, og den vandig-sure opplosning innstilles alkalisk med fast kaliumkarbonat ved 0°, og det utfelte reaksjonsprodukt ekstraheres tilslutt med eddikester. Den organiske fase vaskes nå med mettet natriumklorid-opplosning, torkes over natriumsulfat, og opplosningsmidlet avdampes under forminsket trykk. Det blir en gulaktig, viskos olje tilbake. Denne opploses i lite etanolisk saltsyre. Opplosningsmidlet og den overskytende syre avdampes under forminsket trykk, resten opptas i lite absolutt etanol og fortynnes med eter. Hydrokloridet felles ut, når man lar denne opplosning stå natten over ved 20°. Ved sublimasjon ved 160°/0,001 mm Hg-trykk og en ytterligere omkrystallisasjon fra etanol/eter renses produktet; smeltepunkt 214° (spaltning). 5.0 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one and 1,2 g of sodium methylate in 60 ml of absolute dimethyl sulfoxide and stir the mixture for 18 hours. The reaction solution is then poured into 500 ml of ice-cold water, and the precipitated product is extracted with vinegar. The organic solution is treated with 2-n hydrochloric acid, and the aqueous-acidic solution is made alkaline with solid potassium carbonate at 0°, and the precipitated reaction product is finally extracted with acetic acid. The organic phase is now washed with saturated sodium chloride solution, dried over sodium sulfate, and the solvent is evaporated under reduced pressure. A yellowish, viscous oil remains. This dissolves in a little ethanolic hydrochloric acid. The solvent and the excess acid are evaporated under reduced pressure, the residue is taken up in a little absolute ethanol and diluted with ether. The hydrochloride precipitates when this solution is allowed to stand overnight at 20°. By sublimation at 160°/0.001 mm Hg pressure and a further recrystallization from ethanol/ether, the product is purified; melting point 214° (decomposition).
EKSEMPEL 8 EXAMPLE 8
8-klor-ll-i sopropyl-1,2,3,11,12,12a-heksahydro(4H,6H)pyrido [2,1-c][l,4]benzodiazepin-l2-on-maleat 8-chloro-11-isopropyl-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one maleate
Man suspenderer 25,0 g 8-klor-l,2,3,11,12,12a-heksahydro(4H, 6H)pyrido[2,1-c][l,4]benzodiazepin-l2-on og 5,97 g natriummetylat i 100 ml absolutt dimetylsulfoksyd, oppvarmer blandingen til 100° og rorer ved denne temperatur i 30 minutter. 25.0 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one and 5.97 g of sodium methylate in 100 ml of absolute dimethyl sulphoxide, heat the mixture to 100° and stir at this temperature for 30 minutes.
Man oppnår tilslutt en klar opplosning, som man dråpevis tilsetter ved 100° en opplosning av 18,3 g isopropylbromid i 50 ml absolutt dimetylsulfoksyd. Reaksjonsblandingen rores videre i 15 timer ved 100°. A clear solution is finally obtained, to which a solution of 18.3 g of isopropyl bromide in 50 ml of absolute dimethyl sulphoxide is added dropwise at 100°. The reaction mixture is further stirred for 15 hours at 100°.
Man lar den avkjole, heller den i 500 ml isvann og innstiller den alkalisk ved tilsetning av fast kaliumkarbonat. Det vandige skikt dekanteres, og den gummilignende rest opptas i kloroform, behandles med dyrekull, torkes over natriumsulfat, filtreres, og opplosningsmidlet fjernes under forminsket trykk. Den tilbakeblivende olje opploses i 2-n saltsyre, behandles med dyrekull, filtreres, og filtratet innstilles alkalisk og trekkes ut med kloroform. Etter fordampning av opplosningsmidlet blir en viskos olje tilbake, som destilleres under hoyvakuum. Allow it to cool, pour it into 500 ml of ice water and make it alkaline by adding solid potassium carbonate. The aqueous layer is decanted, and the gummy residue is taken up in chloroform, treated with animal charcoal, dried over sodium sulfate, filtered, and the solvent is removed under reduced pressure. The remaining oil is dissolved in 2-N hydrochloric acid, treated with charcoal, filtered, and the filtrate is made alkaline and extracted with chloroform. After evaporation of the solvent, a viscous oil remains, which is distilled under high vacuum.
Kp. 150 - 155° ved 0,065 mm Hg-trykk. Kp. 150 - 155° at 0.065 mm Hg pressure.
Maleatsaltet fremstilles ved sammensetning av 6,4 g av den frie base og 2,54 g maleinsyre i etanol og fordampning av opplosningsmidlet. Den tilbakeblivende glasslignende masse krystalliseres fra isopropanol og omkrystalliseres; smeltepunkt 157 - 158°. The maleate salt is prepared by combining 6.4 g of the free base and 2.54 g of maleic acid in ethanol and evaporating the solvent. The remaining glass-like mass is crystallized from isopropanol and recrystallized; melting point 157 - 158°.
EKSEMPEL 9 EXAMPLE 9
ll-butyl-8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [ 2, 1- c][ l, 4] benzodiazepin- l2- on- maleat 11-butyl-8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one- maleate
Man suspenderer 25,8 g 8-klor-l,2,3,11,12,12a-heksahydro(4H, 6H)pyrido[2,l-c][l,4]benzodiazepin-l2-on i 100 ml absolutt dimetylsulfoksyd og tilsetter 6,0 g natriummetylat. Deretter oppvarmes til 100° og rores 30 minutter ved denne temperatur. Tilslutt tildrypper man en opplosning av 20,4 g butylbromid i 50 ml absolutt dimetylsulfoksyd dertil og rorer og oppvarmer ytterligere 6 timer. Den avkjolte reaksjonsopplosning helles i isvann, hvorpå et gummilignende bunnfall felles ut.. Det vandige skikt dekanteres og trekkes ut med kloroform. Det klebrige bunnfall opptas i kloroform, og de to kloroformopp-losninger forenes, torkes over natriumsulfat, behandles med dyrekull, filtreres, og opplosningsmidlet fjernes ved fordampning under forminsket trykk. Det blir en olje tilbake, 25.8 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c][1,4]benzodiazepine-12-one are suspended in 100 ml of absolute dimethyl sulfoxide and add 6.0 g of sodium methylate. It is then heated to 100° and stirred for 30 minutes at this temperature. Finally, a solution of 20.4 g of butyl bromide in 50 ml of absolute dimethylsulfoxide is added dropwise and stirred and heated for a further 6 hours. The cooled reaction solution is poured into ice water, after which a rubber-like precipitate precipitates out. The aqueous layer is decanted and extracted with chloroform. The sticky precipitate is taken up in chloroform, and the two chloroform solutions are combined, dried over sodium sulfate, treated with animal charcoal, filtered, and the solvent is removed by evaporation under reduced pressure. There will be an oil back,
hvilken destillerer i hoyvakuum, hvorpå man oppnår en nesten fargelos olje; kp. 154 - 157°/0,1 mm Hg-trykk. 9,5 g av den frie base omsettes i etanol med 3,97 g maleinsyre til maleat. Man fordamper etanolen under forminsket trykk og krystalliserer resten fra isopropanol; smeltepunkt 137 - 138°. which distills in high vacuum, whereupon an almost colorless oil is obtained; kp. 154 - 157°/0.1 mm Hg pressure. 9.5 g of the free base is converted in ethanol with 3.97 g of maleic acid to maleate. The ethanol is evaporated under reduced pressure and the residue is crystallized from isopropanol; melting point 137 - 138°.
EKSEMPEL 10 EXAMPLE 10
ll-benzyl-8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido [ 2, 1- c][ l, 4] benzodiazepin- l2- on- hydroklorid 11-benzyl-8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido [2,1-c][1,4]benzodiazepine-12-one hydrochloride
25 g 8-klor-l,2,3,11,12,12a-heksahydro(4H,6H)pyrido[2,1-c] 25 g of 8-chloro-1,2,3,11,12,12a-hexahydro(4H,6H)pyrido[2,1-c]
[l,4]benzodiazepin-l2-on, 6 g natriummetylat og lOO ml absolutt dimetylsulfoksyd rores sammen ved 100° i ca. 30 minutter, inn- [1,4]benzodiazepine-12-one, 6 g of sodium methylate and 100 ml of absolute dimethyl sulphoxide are stirred together at 100° for approx. 30 minutes, in-
til en klar opplosning oppstår. Deretter tildryppes en opplos- until a clear solution occurs. A solution is then dripped
ning av 18,9 g benzylklorid i 50 ml absolutt dimetylsulfoksyd ved 100°, og opplosningen oppvarmes ytterligere i 5 timer under roring. Man avkjoler den, og heller reaksjonsopplosningen i ca. ning of 18.9 g of benzyl chloride in 50 ml of absolute dimethylsulfoxide at 100°, and the solution is further heated for 5 hours with stirring. It is cooled, and the reaction solution is poured for approx.
500 ml isvann. Det gummilignende bunnfall trekkes ut med kloro- 500 ml of ice water. The gum-like precipitate is extracted with chloro-
form, kloroformekstraktet vaskes med vann, behandles med dyre- form, the chloroform extract is washed with water, treated with animal
kull, filtreres og torkes over natriumsulfat. Opplosnings- charcoal, filtered and dried over sodium sulfate. dissolution
midlet fjernes deretter under forminsket trykk, og den tilbake- the agent is then removed under reduced pressure, and the
blivende olje destilleres under hoyvakuum; kp. 180°/0,008 mm Hg-trykk. Den erholdte olje omdannes med etanolisk saltsyre remaining oil is distilled under high vacuum; kp. 180°/0.008 mm Hg pressure. The oil obtained is converted with ethanolic hydrochloric acid
til hydroklorid og omkrystalliseres fra etanol. Smeltepunkt 200 - 20 2° (spaltning) . to hydrochloride and recrystallized from ethanol. Melting point 200 - 20 2° (decomposition) .
Claims (1)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO865183A NO163597C (en) | 1986-12-19 | 1986-12-19 | CONTROL DEVICE FOR A ONE OR TWO TRACKED TOOL. |
EP19880900880 EP0334893A1 (en) | 1986-12-19 | 1987-12-18 | Steering system for a one or two track vehicles |
PCT/EP1987/000801 WO1988004565A2 (en) | 1986-12-19 | 1987-12-18 | Steering system for a one or two track vehicles |
AU11559/88A AU1155988A (en) | 1986-12-19 | 1987-12-18 | Steering system for a one or two track vehicles |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO865183A NO163597C (en) | 1986-12-19 | 1986-12-19 | CONTROL DEVICE FOR A ONE OR TWO TRACKED TOOL. |
Publications (4)
Publication Number | Publication Date |
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NO865183D0 NO865183D0 (en) | 1986-12-19 |
NO865183L NO865183L (en) | 1988-06-20 |
NO163597B true NO163597B (en) | 1990-03-19 |
NO163597C NO163597C (en) | 1990-06-27 |
Family
ID=19889502
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO865183A NO163597C (en) | 1986-12-19 | 1986-12-19 | CONTROL DEVICE FOR A ONE OR TWO TRACKED TOOL. |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0334893A1 (en) |
AU (1) | AU1155988A (en) |
NO (1) | NO163597C (en) |
WO (1) | WO1988004565A2 (en) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
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US4955626A (en) * | 1988-01-28 | 1990-09-11 | Smith Eric O M | Skateboards |
JPH04500916A (en) * | 1988-08-01 | 1992-02-20 | クビエルシュキー,ステファン | Movable elements, in particular chassis devices for movable elements for roller skates and movable elements used in the chassis |
FR2656228B1 (en) * | 1989-12-21 | 1992-05-15 | Lt Jp Alexis De Tocqueville | DEVICE FOR JOINING A RUNNING UNIT AS WELL AS A VEHICLE, PARTICULARLY A SKATEBOARD EQUIPPED WITH AT LEAST ONE SUCH DEVICE. |
DE4013018C2 (en) * | 1990-04-24 | 2000-12-07 | Stefan Kubierschky | Roller sports equipment |
ES2393199T3 (en) | 2004-11-19 | 2012-12-19 | Scarpar Pty Ltd | Motorized personal transport vehicle |
RU2606862C2 (en) * | 2016-03-10 | 2017-01-10 | Анатолий Степанович Дресвянкин | Sport-pleasure vehicle reclining on skis and skates, das systems |
CN106964144A (en) * | 2017-03-29 | 2017-07-21 | 中山市元亨家居用品有限公司 | Skateboard frame with shock-absorbing function and scooter with same |
CN106964143A (en) * | 2017-03-29 | 2017-07-21 | 中山市元亨家居用品有限公司 | Scooter |
CN106955482A (en) * | 2017-03-29 | 2017-07-18 | 中山市元亨家居用品有限公司 | Scooter wheel carrier and scooter with same |
CN108421244A (en) * | 2017-03-29 | 2018-08-21 | 中山市元亨家居用品有限公司 | A kind of scooter |
CN108310751A (en) * | 2018-01-22 | 2018-07-24 | 中山市元亨家居用品有限公司 | Sport skateboard |
CN108465230A (en) * | 2018-05-23 | 2018-08-31 | 中山市元亨家居用品有限公司 | Scooter |
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FR410240A (en) * | 1909-12-11 | 1910-05-14 | Arthur Pomeroy | Roller Skate Improvements |
CH202577A (en) * | 1938-08-22 | 1939-01-31 | Pietroboni Silvio | Roller skate. |
US3862736A (en) * | 1973-01-04 | 1975-01-28 | Dearborn Rubber Corp | Device for forming polygonal voids in concrete members |
FR2423243A1 (en) * | 1978-04-19 | 1979-11-16 | Morys Raymond | Board for moving on snow slopes - with two skis attached underneath fitted with silentblocs |
US4337961A (en) * | 1979-11-16 | 1982-07-06 | Covert William J | Skateboard |
-
1986
- 1986-12-19 NO NO865183A patent/NO163597C/en unknown
-
1987
- 1987-12-18 WO PCT/EP1987/000801 patent/WO1988004565A2/en not_active Application Discontinuation
- 1987-12-18 EP EP19880900880 patent/EP0334893A1/en not_active Withdrawn
- 1987-12-18 AU AU11559/88A patent/AU1155988A/en not_active Abandoned
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Publication number | Publication date |
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WO1988004565A3 (en) | 1988-08-11 |
EP0334893A1 (en) | 1989-10-04 |
NO865183D0 (en) | 1986-12-19 |
NO163597C (en) | 1990-06-27 |
AU1155988A (en) | 1988-07-15 |
NO865183L (en) | 1988-06-20 |
WO1988004565A2 (en) | 1988-06-30 |
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