SE437029B - Analogiforfarande for framstellning av derivat av imidazo/1,5-a//1,4/bensodiazepin - Google Patents

Analogiforfarande for framstellning av derivat av imidazo/1,5-a//1,4/bensodiazepin

Info

Publication number: SE437029B
Authority: SE; Sweden
Prior art keywords: formula; compound; group; meaning given; given above
Prior art date: 1977-03-11

Application number

SE7802787A

Other languages

English (en)

Swedish (sv)

Other versions

SE7802787L (sv

Inventor

A Walser

R I Fryer

L Benjamin

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1977-03-11

Filing date

1978-03-10

Publication date

1985-02-04

1978-03-10 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1978-09-12 Publication of SE7802787L publication Critical patent/SE7802787L/xx

1985-02-04 Publication of SE437029B publication Critical patent/SE437029B/sv

Links

238000000034 method Methods 0.000 title claims description 15
229940049706 benzodiazepine Drugs 0.000 title description 3
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title 1
ONOBXDPYDHTSBQ-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-diazepine Chemical compound C1CC=CCNN1 ONOBXDPYDHTSBQ-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 122
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 42
-1 alkali metal alkoxide Chemical class 0.000 claims description 35
238000002360 preparation method Methods 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 31
239000000203 mixture Substances 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 28
239000000460 chlorine Substances 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 21
150000002367 halogens Chemical group 0.000 claims description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 15
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 10
229910052783 alkali metal Inorganic materials 0.000 claims description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 8
150000002431 hydrogen Chemical group 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
229910052757 nitrogen Inorganic materials 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
238000005915 ammonolysis reaction Methods 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
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 claims description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 2
XKZXEVFCCLDIOO-UHFFFAOYSA-N methyl 8-chloro-6-(2-chlorophenyl)-1-methoxy-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound COC(=O)C=1N=C(OC)N(C2=CC=C(Cl)C=C22)C=1CN=C2C1=CC=CC=C1Cl XKZXEVFCCLDIOO-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
101000988966 Escherichia coli Heat-stable enterotoxin A3/A4 Proteins 0.000 claims 1
229940100198 alkylating agent Drugs 0.000 claims 1
239000002168 alkylating agent Substances 0.000 claims 1
229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims 1
150000001557 benzodiazepines Chemical class 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
239000001301 oxygen Substances 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 158
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
238000006243 chemical reaction Methods 0.000 description 54
239000000243 solution Substances 0.000 description 52
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
238000004458 analytical method Methods 0.000 description 32
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
239000007787 solid Substances 0.000 description 26
239000002904 solvent Substances 0.000 description 26
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 20
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
239000013078 crystal Substances 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
238000003756 stirring Methods 0.000 description 15
239000002253 acid Substances 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000001953 recrystallisation Methods 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 10
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
238000002425 crystallisation Methods 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
230000008025 crystallization Effects 0.000 description 9
239000012467 final product Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
239000000908 ammonium hydroxide Substances 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
150000002170 ethers Chemical class 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
239000000047 product Substances 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
239000002775 capsule Substances 0.000 description 5
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 5
238000001035 drying Methods 0.000 description 5
150000003462 sulfoxides Chemical class 0.000 description 5
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000003973 alkyl amines Chemical class 0.000 description 4
239000002585 base Substances 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000006260 foam Substances 0.000 description 4
239000000499 gel Substances 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
235000019759 Maize starch Nutrition 0.000 description 3
229920000881 Modified starch Polymers 0.000 description 3
229910000831 Steel Inorganic materials 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
239000000376 reactant Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
150000003334 secondary amides Chemical class 0.000 description 3
239000010959 steel Substances 0.000 description 3
150000003457 sulfones Chemical class 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 2
KWYUZJRDLHNOOW-UHFFFAOYSA-N 1H-1,4-benzodiazepine-3-carboxamide Chemical compound C1=NC(C(=O)N)=CNC2=CC=CC=C21 KWYUZJRDLHNOOW-UHFFFAOYSA-N 0.000 description 2
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 2
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
239000004368 Modified starch Substances 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
FQYUMYWMJTYZTK-UHFFFAOYSA-N Phenyl glycidyl ether Chemical compound C1OC1COC1=CC=CC=C1 FQYUMYWMJTYZTK-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
LSQOUBKWMBDIPL-UHFFFAOYSA-N [7-chloro-5-(2-fluorophenyl)-2,3-dihydro-1h-1,4-benzodiazepin-2-yl]methanamine Chemical compound C12=CC(Cl)=CC=C2NC(CN)CN=C1C1=CC=CC=C1F LSQOUBKWMBDIPL-UHFFFAOYSA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
FQMHULUCKSVAOZ-UHFFFAOYSA-N methyl 1H-1-benzazepine-3-carboxylate Chemical compound COC(=O)C1=CNC2=C(C=C1)C=CC=C2 FQMHULUCKSVAOZ-UHFFFAOYSA-N 0.000 description 2
229940050176 methyl chloride Drugs 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
235000019426 modified starch Nutrition 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
150000004967 organic peroxy acids Chemical class 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
150000003140 primary amides Chemical class 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000000126 substance Substances 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
150000003511 tertiary amides Chemical class 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
UFMKRXZAUYLACF-UHFFFAOYSA-N 1,3-benzodiazepine-3-carboxamide Chemical compound N1=CN(C=CC2=C1C=CC=C2)C(=O)N UFMKRXZAUYLACF-UHFFFAOYSA-N 0.000 description 1
VUMCYGBPHCVIAY-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxamide Chemical compound NC(=O)C1=NNc2ccccc2C=C1 VUMCYGBPHCVIAY-UHFFFAOYSA-N 0.000 description 1
OSZOJXPLWNBWLQ-UHFFFAOYSA-N 1h-1,2-benzodiazepine-5-carboxamide Chemical compound NC(=O)C1=CC=NNC2=CC=CC=C12 OSZOJXPLWNBWLQ-UHFFFAOYSA-N 0.000 description 1
OQXHYLPBIFWMNR-UHFFFAOYSA-N 1h-1-benzazepine-3-carboxamide Chemical compound C1=CC(C(=O)N)=CNC2=CC=CC=C21 OQXHYLPBIFWMNR-UHFFFAOYSA-N 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
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
YOUPYQXYULGKCB-UHFFFAOYSA-N COC(=O)C1=NNC=CC=C1 Chemical compound COC(=O)C1=NNC=CC=C1 YOUPYQXYULGKCB-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
101000952234 Homo sapiens Sphingolipid delta(4)-desaturase DES1 Proteins 0.000 description 1
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 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
150000001204 N-oxides Chemical class 0.000 description 1
UMHFCPGRAIOVMR-UHFFFAOYSA-N N1C=CC=C(C2=C1C=CC=C2)C(=O)OC Chemical class N1C=CC=C(C2=C1C=CC=C2)C(=O)OC UMHFCPGRAIOVMR-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
238000003723 Smelting Methods 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
102100037416 Sphingolipid delta(4)-desaturase DES1 Human genes 0.000 description 1
229920002472 Starch Polymers 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
229910052770 Uranium Inorganic materials 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
238000007605 air drying Methods 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
229940005530 anxiolytics Drugs 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
125000005518 carboxamido group Chemical group 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
238000002649 immunization Methods 0.000 description 1
230000003053 immunization Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
NXEOSYTZUZQNOY-UHFFFAOYSA-N methyl 1,8-dichloro-6-(2-chlorophenyl)-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound COC(=O)C=1N=C(Cl)N(C2=CC=C(Cl)C=C22)C=1CN=C2C1=CC=CC=C1Cl NXEOSYTZUZQNOY-UHFFFAOYSA-N 0.000 description 1
PQEYKXSDTLGGIB-UHFFFAOYSA-N methyl 1H-1,2-benzodiazepine-3-carboxylate Chemical compound N1N=C(C=CC2=C1C=CC=C2)C(=O)OC PQEYKXSDTLGGIB-UHFFFAOYSA-N 0.000 description 1
JNZOSRLQELVQCA-UHFFFAOYSA-N methyl 1H-1,4-benzodiazepine-3-carboxylate Chemical compound COC(=O)C=1N=CC2=C(NC=1)C=CC=C2 JNZOSRLQELVQCA-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
229940035363 muscle relaxants Drugs 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
238000000197 pyrolysis Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000000523 sample Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
235000015067 sauces Nutrition 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
238000000527 sonication Methods 0.000 description 1
241000894007 species Species 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000001648 tannin Substances 0.000 description 1
229920001864 tannin Polymers 0.000 description 1
235000018553 tannin Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000002834 transmittance Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
- 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
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SE7802787A 1977-03-11 1978-03-10 Analogiforfarande for framstellning av derivat av imidazo/1,5-a//1,4/bensodiazepin SE437029B (sv)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/776,820 US4125726A (en)	1977-03-11	1977-03-11	Imidazo[1,5-a][1,4]benzodiazepines

Publications (2)

Publication Number	Publication Date
SE7802787L SE7802787L (sv)	1978-09-12
SE437029B true SE437029B (sv)	1985-02-04

Family

ID=25108467

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SE7802787A SE437029B (sv)	1977-03-11	1978-03-10	Analogiforfarande for framstellning av derivat av imidazo/1,5-a//1,4/bensodiazepin

Country Status (13)

Country	Link
US (3)	US4125726A (fr)
JP (1)	JPS53112897A (fr)
AU (1)	AU516873B2 (fr)
BE (1)	BE864809A (fr)
CA (1)	CA1093073A (fr)
CH (1)	CH638208A5 (fr)
DE (1)	DE2810476A1 (fr)
DK (1)	DK108078A (fr)
FR (1)	FR2383183A1 (fr)
GB (1)	GB1594867A (fr)
NL (1)	NL7802675A (fr)
SE (1)	SE437029B (fr)
ZA (1)	ZA781384B (fr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4280957A (en) *	1974-09-11	1981-07-28	Hoffmann-La Roche Inc.	Imidazodiazepines and processes therefor
DE2754112A1 (de) *	1977-12-05	1979-06-13	Kali Chemie Pharma Gmbh	1,4-benzodiazepinderivate, ihre salze und diese verbindungen enthaltende arzneipraeparate
US4226768A (en) *	1979-05-29	1980-10-07	Hoffmann-La Roche Inc.	Process for the preparation of imidazobenzodiazepines
US4259241A (en) *	1979-05-29	1981-03-31	Hoffmann-La Roche Inc.	Process for the preparation of imidazobenzodiazepines
US4226771A (en) *	1979-07-25	1980-10-07	Hoffmann-La Roche Inc.	1,2,5-Oxadiazino[5,4-a][1,4]benzodiazepine derivatives
US4250095A (en) *	1979-07-25	1981-02-10	Hoffmann-La Roche Inc.	Imidazobenzodiazepines
US4238610A (en) *	1979-12-20	1980-12-09	Hoffmann-La Roche Inc.	Intermediates for the production of imidazobenzodiazepines
US4247463A (en) *	1980-04-11	1981-01-27	Hoffmann-La Roche Inc.	Process for the preparation of imidazobenzodiazepines
ZA845757B (en) *	1983-08-25	1985-04-24	Hoffmann La Roche	Benzodiazepine derivatives
DE102007035350A1 (de) *	2007-07-27	2009-01-29	Dr. Ing. H.C. F. Porsche Aktiengesellschaft	Förderleitung für ein Hydrauliksystem und Hydrauliksystem
CN109790170B (zh)	2016-08-16	2022-08-02	Uwm研究基金会有限公司	Gaba(a)受体调节剂和控制哮喘中气道高反应性和炎症的方法
UY37556A (es)	2017-01-10	2018-07-31	Bayer Ag	Derivados heterocíclicos como pesticidas
AR113206A1 (es)	2017-01-10	2020-02-19	Bayer Cropscience Ag	Derivados heterocíclicos como pesticidas
TWI820231B (zh)	2018-10-11	2023-11-01	德商拜耳廠股份有限公司	用於製備經取代咪唑衍生物之方法
KR20230039665A (ko)	2020-07-02	2023-03-21	바이엘 악티엔게젤샤프트	해충 방제제로서의 헤테로사이클 유도체
WO2025026738A1 (fr)	2023-07-31	2025-02-06	Bayer Aktiengesellschaft	Dérivés de 6-[5-(éthylsulfonyl)-1-méthyl-1h-imidazol-4-yl]-7-méthyl-3-(pentafluoroéthyl)-7h-imidazo [4,5-c]pyridazine en tant que pesticides

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3852461A (en) *	1971-08-04	1974-12-03	Upjohn Co	Benzodiapines used as minor tranquilizers
US3763179A (en) *	1972-05-05	1973-10-02	Upjohn Co	2-imidazol-1-yl benzophenones
ZA755418B (en) *	1974-09-11	1977-06-29	Hoffmann La Roche	Diazepine derivatives
US3910946A (en) *	1974-09-12	1975-10-07	Upjohn Co	4H-Imidazo{8 1,2-a{9 {8 1,4{9 benzodiazepines
DE2609486A1 (de) *	1975-08-07	1977-05-12	Hoffmann La Roche	Imidazo eckige klammer auf 1,5-a eckige klammer zu eckige klammer auf 1,4 eckige klammer zu diazepin-verbindungen und verfahren zu ihrer herstellung
US4005099A (en) *	1975-11-21	1977-01-25	The Upjohn Company	1-[(Dimethylamino)-methyl]-6-aryl-4H-imidazo[1,5-a][1,4]benzodiazepines

1977
- 1977-03-11 US US05/776,820 patent/US4125726A/en not_active Expired - Lifetime
1978
- 1978-03-09 ZA ZA00781384A patent/ZA781384B/xx unknown
- 1978-03-09 CH CH257578A patent/CH638208A5/de not_active IP Right Cessation
- 1978-03-10 DK DK108078A patent/DK108078A/da not_active Application Discontinuation
- 1978-03-10 GB GB9577/78A patent/GB1594867A/en not_active Expired
- 1978-03-10 SE SE7802787A patent/SE437029B/sv not_active IP Right Cessation
- 1978-03-10 AU AU34056/78A patent/AU516873B2/en not_active Expired
- 1978-03-10 NL NL7802675A patent/NL7802675A/xx not_active Application Discontinuation
- 1978-03-10 JP JP2675478A patent/JPS53112897A/ja active Pending
- 1978-03-10 DE DE19782810476 patent/DE2810476A1/de not_active Ceased
- 1978-03-10 CA CA298,645A patent/CA1093073A/fr not_active Expired
- 1978-03-10 FR FR7806983A patent/FR2383183A1/fr active Granted
- 1978-03-13 BE BE185863A patent/BE864809A/fr not_active IP Right Cessation
- 1978-07-27 US US05/928,479 patent/US4146722A/en not_active Expired - Lifetime
- 1978-07-27 US US05/928,765 patent/US4147875A/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CH638208A5 (de)	1983-09-15
BE864809A (fr)	1978-09-13
FR2383183A1 (fr)	1978-10-06
DK108078A (da)	1978-09-12
US4146722A (en)	1979-03-27
US4147875A (en)	1979-04-03
ZA781384B (en)	1979-02-28
NL7802675A (nl)	1978-09-13
DE2810476A1 (de)	1978-09-14
SE7802787L (sv)	1978-09-12
FR2383183B1 (fr)	1980-06-06
CA1093073A (fr)	1981-01-06
US4125726A (en)	1978-11-14
JPS53112897A (en)	1978-10-02
GB1594867A (en)	1981-08-05
AU3405678A (en)	1979-09-13
AU516873B2 (en)	1981-06-25

Legal Events

Date

Code

Title

Description

1995-01-31

NUG

Patent has lapsed

Ref document number: 7802787-7

Effective date: 19890426

Format of ref document f/p: F

Publication	Publication Date	Title
SE437029B (sv)	1985-02-04	Analogiforfarande for framstellning av derivat av imidazo/1,5-a//1,4/bensodiazepin
DK168073B1 (da)	1994-01-31	Analogifremgangsmaade til fremstilling af imidazodiazepiner eller farmaceutisk acceptable syreadditionssalte deraf
KR900003496B1 (ko)	1990-05-21	티에닐 축합 피라졸 유도체의 제조방법
Bergman et al.	2003	Studies of the reactions between indole-2, 3-diones (isatins) and 2-aminobenzylamine
Alexandre et al.	2003	Novel series of 8H-quinazolino [4, 3-b] quinazolin-8-ones via two Niementowski condensations
PL101248B1 (pl)	1978-12-30	Sposob wytwarzania nowych pochodnych piroliny
CA2258885A1 (fr)	1997-12-31	Les benzazepines: des antagonistes tricycliques de la vasopressine
DK161968B (da)	1991-09-02	Analogifremgangsmaade til fremstilling af imidazo-pyrazolo-pyrimidiner eller farmaceutisk acceptable salte deraf
CH630381A5 (de)	1982-06-15	Verfahren zur herstellung von diazepinderivaten.
Kotovshchikov et al.	2023	Divergent cyclization of 2-(5-iodo-1, 2, 3-triazolyl) benzamides toward triazole-fused lactams and cyclic imidates
DK145577B (da)	1982-12-13	Analogifremgangsmaade til fremstilling af s-triazolo(4,3-a)-(1,4)-benzodiazepiner eller 5n-oxyder eller syreadditionssalte deraf
US3573308A (en)	1971-03-30	3-lower alkoxy methyl-3,4-dihydro-4-hydroxy-4-aryl quinazolin-2(1h) ones and related compounds
Newhouse et al.	1992	Novel [3+ 2] and [3+ 3] 4-quinolone annulations by tandem Claisen-Cope amidoalkylation reaction
Papadopoulou et al.	2021	Intramolecular Diels-Alder reactions of 1, 2, 4-triazines. Synthesis of 3-alkylpyridines via Raney nickel desulfurization of thieno [2, 3-b] pyridines
Keshipour et al.	2015	A novel one-pot isocyanide-based three-component reaction: synthesis of highly functionalized imidazo-chromen-4-ones
Grossi et al.	1993	1, 5-Benzodiazepines XI. 5-(Dialkylamino) or 5-(alkylthio) substituted 8-chloro-6-phenyl-6H-[1, 2, 4] triazolo [4, 3-a][1, 5] benzodiazepines with anticonvulsant activity
EP0072029B1 (fr)	1986-10-22	Triazolobenzazépines, procédé et intermédiaires pour leur fabrication et médicaments les contenant
Sączewski et al.	2005	Synthesis of 2, 3-dihydroimidazo [1, 2-a] pyrimidin-5 (1H)-ones by the domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates
Huckle et al.	1971	4-Amino-2, 3, 4, 5-tetrahydro-1-benzoxepin-5-ols, 4-amino-2, 3, 4, 5-tetrahydro-1-benzothiepin-5-ols, and related compounds
Grintsevich et al.	2022	An Attempt to Achieve Hydrated Imidazoline Ring Expansion (HIRE) of Diarene-Fused [1, 4] Diazepinones Delivers Selective Dopamine D2 Receptor Ligands
US3513158A (en)	1970-05-19	Process for preparing 5-aryl benzodiazepines and intermediates
IE43762B1 (en)	1981-05-20	Diazepine derivatives
DK156391B (da)	1989-08-14	Analogifremgangsmaade til fremstilling af 3-aminopyrrolderivater
IL42947A (en)	1977-01-31	Process for the preparation of 1,3-dihydro-2h-1,4-benzodiazepin-2-ones
US3886144A (en)	1975-05-27	Oxazolo(and oxazino)(3,2-d)pyrazolo-(3,4-f)(1,4)diazepin-5(6H)-one compounds