JPS6249273B2 - - Google Patents

Info

Publication number: JPS6249273B2
Authority: JP; Japan
Prior art keywords: formula; lower alkyl; group; phenyl; hydrogen
Prior art date: 1975-08-07
Legal status (The legal status 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 status listed.): Expired

Application number

JP51073932A

Other languages

English (en)

Japanese (ja)

Other versions

JPS5219697A (en

Inventor

Warusaa Aamin

Ian Furaiyaa Rodonii

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

F Hoffmann La Roche AG

Original Assignee

F Hoffmann La Roche AG

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.)

1975-08-07

Filing date

1976-06-24

Publication date

1987-10-19

1976-06-24 Application filed by F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG

1977-02-15 Publication of JPS5219697A publication Critical patent/JPS5219697A/ja

1987-10-19 Publication of JPS6249273B2 publication Critical patent/JPS6249273B2/ja

Status Granted legal-status Critical Current

Links

125000000217 alkyl group Chemical group 0.000 claims description 339
150000001875 compounds Chemical class 0.000 claims description 324
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 189
229910052739 hydrogen Inorganic materials 0.000 claims description 172
239000001257 hydrogen Substances 0.000 claims description 172
238000006243 chemical reaction Methods 0.000 claims description 149
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 111
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 106
150000003839 salts Chemical class 0.000 claims description 92
-1 cyano, cyanomethyl Chemical group 0.000 claims description 88
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
239000002904 solvent Substances 0.000 claims description 74
125000004076 pyridyl group Chemical group 0.000 claims description 61
229940049706 benzodiazepine Drugs 0.000 claims description 56
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 52
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 51
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 51
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 48
125000004093 cyano group Chemical group *C#N 0.000 claims description 45
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
239000002253 acid Substances 0.000 claims description 43
229910052736 halogen Inorganic materials 0.000 claims description 40
150000002367 halogens Chemical class 0.000 claims description 39
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 34
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
125000003282 alkyl amino group Chemical group 0.000 claims description 30
238000004519 manufacturing process Methods 0.000 claims description 27
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 26
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 25
MZHUTGQZAZLFKW-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxylic acid Chemical compound C1=CC(C(=O)O)=NNC2=CC=CC=C21 MZHUTGQZAZLFKW-UHFFFAOYSA-N 0.000 claims description 22
238000000034 method Methods 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 21
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 20
125000005843 halogen group Chemical group 0.000 claims description 19
239000003054 catalyst Substances 0.000 claims description 18
125000004423 acyloxy group Chemical group 0.000 claims description 17
238000007254 oxidation reaction Methods 0.000 claims description 17
230000003647 oxidation Effects 0.000 claims description 16
VUMCYGBPHCVIAY-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carboxamide Chemical compound NC(=O)C1=NNc2ccccc2C=C1 VUMCYGBPHCVIAY-UHFFFAOYSA-N 0.000 claims description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 15
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 12
238000010438 heat treatment Methods 0.000 claims description 12
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 12
150000004703 alkoxides Chemical class 0.000 claims description 10
239000003153 chemical reaction reagent Substances 0.000 claims description 9
230000014509 gene expression Effects 0.000 claims description 9
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 8
229910052783 alkali metal Inorganic materials 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
125000001246 bromo group Chemical group Br* 0.000 claims description 6
150000003857 carboxamides Chemical class 0.000 claims description 6
238000005984 hydrogenation reaction Methods 0.000 claims description 6
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
238000006698 hydrazinolysis reaction Methods 0.000 claims description 4
229910052744 lithium Inorganic materials 0.000 claims description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 4
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 3
125000004849 alkoxymethyl group Chemical group 0.000 claims description 3
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
238000005915 ammonolysis reaction Methods 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 3
VEDQGLSZFGZSAO-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide Chemical compound NC(=O)C=1N=CN(C2=CC=C(Cl)C=C22)C=1CN=C2C1=CC=CC=C1F VEDQGLSZFGZSAO-UHFFFAOYSA-N 0.000 claims description 2
125000005042 acyloxymethyl group Chemical group 0.000 claims description 2
125000003172 aldehyde group Chemical group 0.000 claims description 2
125000005262 alkoxyamine group Chemical group 0.000 claims description 2
239000011230 binding agent Substances 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
125000004970 halomethyl group Chemical group 0.000 claims description 2
239000000932 sedative agent Substances 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 36
IMXWNWBXKWASOM-UHFFFAOYSA-N 3h-imidazo[1,5-a][1,4]diazepine Chemical class N1=CC=CN2CN=CC2=C1 IMXWNWBXKWASOM-UHFFFAOYSA-N 0.000 claims 18
125000005059 halophenyl group Chemical group 0.000 claims 15
125000005236 alkanoylamino group Chemical group 0.000 claims 5
125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 claims 5
239000004480 active ingredient Substances 0.000 claims 3
AXDNGJPEZJTYAN-UHFFFAOYSA-N 1h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound N1=CC2=CC=CC=C2N2CN=CC2=C1 AXDNGJPEZJTYAN-UHFFFAOYSA-N 0.000 claims 1
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
239000012024 dehydrating agents‎ Substances 0.000 claims 1
125000001207 fluorophenyl group Chemical group 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims 1
230000001624 sedative effect Effects 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 537
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 266
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 263
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 258
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 212
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 209
239000000203 mixture Substances 0.000 description 180
239000000243 solution Substances 0.000 description 171
238000002844 melting Methods 0.000 description 164
230000008018 melting Effects 0.000 description 164
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 156
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 147
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 108
238000003756 stirring Methods 0.000 description 96
239000013078 crystal Substances 0.000 description 83
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 70
238000004458 analytical method Methods 0.000 description 60
229960000583 acetic acid Drugs 0.000 description 59
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 52
239000007788 liquid Substances 0.000 description 50
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 46
239000011541 reaction mixture Substances 0.000 description 46
239000007787 solid Substances 0.000 description 45
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000000047 product Substances 0.000 description 42
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 41
238000010992 reflux Methods 0.000 description 41
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
239000000523 sample Substances 0.000 description 40
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 31
150000002430 hydrocarbons Chemical group 0.000 description 31
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000012442 inert solvent Substances 0.000 description 30
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 30
229930195733 hydrocarbon Natural products 0.000 description 28
150000002170 ethers Chemical class 0.000 description 27
239000000741 silica gel Substances 0.000 description 25
229910002027 silica gel Inorganic materials 0.000 description 25
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
239000012074 organic phase Substances 0.000 description 23
239000000725 suspension Substances 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
238000000354 decomposition reaction Methods 0.000 description 21
238000001914 filtration Methods 0.000 description 21
239000012362 glacial acetic acid Substances 0.000 description 21
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 20
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 19
239000010410 layer Substances 0.000 description 19
229910052757 nitrogen Inorganic materials 0.000 description 19
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
238000002425 crystallisation Methods 0.000 description 17
230000008025 crystallization Effects 0.000 description 17
125000001188 haloalkyl group Chemical group 0.000 description 17
239000000284 extract Substances 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
229910052786 argon Inorganic materials 0.000 description 15
235000010288 sodium nitrite Nutrition 0.000 description 15
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 14
125000002252 acyl group Chemical group 0.000 description 14
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 14
239000002480 mineral oil Substances 0.000 description 14
235000010446 mineral oil Nutrition 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 13
WCVOGSZTONGSQY-UHFFFAOYSA-N 2,4,6-trichloroanisole Chemical compound COC1=C(Cl)C=C(Cl)C=C1Cl WCVOGSZTONGSQY-UHFFFAOYSA-N 0.000 description 13
239000000538 analytical sample Substances 0.000 description 13
238000009835 boiling Methods 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
239000000126 substance Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
150000001298 alcohols Chemical class 0.000 description 12
239000007864 aqueous solution Substances 0.000 description 12
125000003118 aryl group Chemical group 0.000 description 12
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 12
238000001816 cooling Methods 0.000 description 12
125000000623 heterocyclic group Chemical group 0.000 description 12
239000000463 material Substances 0.000 description 12
229910000029 sodium carbonate Inorganic materials 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
125000002768 hydroxyalkyl group Chemical group 0.000 description 11
150000007524 organic acids Chemical class 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
229910000104 sodium hydride Inorganic materials 0.000 description 11
238000012360 testing method Methods 0.000 description 11
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 10
239000007868 Raney catalyst Substances 0.000 description 10
229910000564 Raney nickel Inorganic materials 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
230000010933 acylation Effects 0.000 description 10
238000005917 acylation reaction Methods 0.000 description 10
125000003342 alkenyl group Chemical group 0.000 description 10
239000005457 ice water Substances 0.000 description 10
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 10
230000009467 reduction Effects 0.000 description 10
238000006722 reduction reaction Methods 0.000 description 10
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 10
239000000052 vinegar Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
241000699670 Mus sp. Species 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
239000003921 oil Substances 0.000 description 9
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
238000001953 recrystallisation Methods 0.000 description 9
235000021419 vinegar Nutrition 0.000 description 9
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 8
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 8
150000001204 N-oxides Chemical class 0.000 description 8
GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 8
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 8
229910021529 ammonia Inorganic materials 0.000 description 8
239000000908 ammonium hydroxide Substances 0.000 description 8
239000002585 base Substances 0.000 description 8
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 8
238000011065 in-situ storage Methods 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
239000011734 sodium Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
150000008065 acid anhydrides Chemical class 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
239000012141 concentrate Substances 0.000 description 7
239000006185 dispersion Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
229950004696 flusalan Drugs 0.000 description 7
239000006260 foam Substances 0.000 description 7
229940093915 gynecological organic acid Drugs 0.000 description 7
VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 7
235000019392 nitrosyl chloride Nutrition 0.000 description 7
235000005985 organic acids Nutrition 0.000 description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
239000004157 Nitrosyl chloride Substances 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
239000000370 acceptor Substances 0.000 description 6
125000001769 aryl amino group Chemical group 0.000 description 6
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
229910000041 hydrogen chloride Inorganic materials 0.000 description 6
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
238000007034 nitrosation reaction Methods 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
BQPUZODTKSPSQX-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carbaldehyde Chemical compound O=CC1=NNc2ccccc2C=C1 BQPUZODTKSPSQX-UHFFFAOYSA-N 0.000 description 5
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 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
241000282326 Felis catus Species 0.000 description 5
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
150000001299 aldehydes Chemical group 0.000 description 5
125000001931 aliphatic group Chemical group 0.000 description 5
125000003710 aryl alkyl group Chemical group 0.000 description 5
125000005605 benzo group Chemical group 0.000 description 5
238000007865 diluting Methods 0.000 description 5
239000003480 eluent Substances 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000012467 final product Substances 0.000 description 5
150000002576 ketones Chemical class 0.000 description 5
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 5
229940050176 methyl chloride Drugs 0.000 description 5
239000002808 molecular sieve Substances 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000012047 saturated solution Substances 0.000 description 5
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 4
UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 4
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
229940126062 Compound A Drugs 0.000 description 4
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
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 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
GUGCLZQUEANZKP-UHFFFAOYSA-N OC(=O)C1=NNC=CC=C1 Chemical compound OC(=O)C1=NNC=CC=C1 GUGCLZQUEANZKP-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 4
238000000297 Sandmeyer reaction Methods 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
229910052776 Thorium Inorganic materials 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
238000007605 air drying Methods 0.000 description 4
150000001450 anions Chemical class 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
238000006114 decarboxylation reaction Methods 0.000 description 4
238000004090 dissolution Methods 0.000 description 4
238000001035 drying Methods 0.000 description 4
150000002169 ethanolamines Chemical class 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
239000011976 maleic acid Substances 0.000 description 4
150000004702 methyl esters Chemical class 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
230000033764 rhythmic process Effects 0.000 description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
HNDGEYCCZGRMTN-UHFFFAOYSA-N thieno[3,2-f:4,5-f]bis[1]benzothiophene Chemical compound S1C2=CC=3SC=CC=3C=C2C2=C1C=C(SC=C1)C1=C2 HNDGEYCCZGRMTN-UHFFFAOYSA-N 0.000 description 4
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 3
GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 3
GWSTUUNCARBYBG-UHFFFAOYSA-N 2-ethylbutanamide;propanedioic acid Chemical compound OC(=O)CC(O)=O.CCC(CC)C(N)=O GWSTUUNCARBYBG-UHFFFAOYSA-N 0.000 description 3
DEVCMVPFFSCNDT-UHFFFAOYSA-N 8-chloro-6-(2-chlorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC(C(N)=O)=C2CN=C1C1=CC=CC=C1Cl DEVCMVPFFSCNDT-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
125000005041 acyloxyalkyl group Chemical group 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
229910052782 aluminium Inorganic materials 0.000 description 3
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 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
229940079593 drug Drugs 0.000 description 3
229960003750 ethyl chloride Drugs 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
239000007789 gas Substances 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
238000005658 halogenation reaction Methods 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
239000000155 melt Substances 0.000 description 3
FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
230000009935 nitrosation Effects 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
150000002905 orthoesters Chemical class 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
238000005192 partition Methods 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000002994 raw material Substances 0.000 description 3
230000035939 shock Effects 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000010998 test method Methods 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
125000003944 tolyl group Chemical group 0.000 description 3
230000009466 transformation Effects 0.000 description 3
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-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
XTOQMDCHFVDCCL-UHFFFAOYSA-N 4-[chloro(morpholin-4-yl)phosphoryl]morpholine Chemical compound C1COCCN1P(=O)(Cl)N1CCOCC1 XTOQMDCHFVDCCL-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
YOUPYQXYULGKCB-UHFFFAOYSA-N COC(=O)C1=NNC=CC=C1 Chemical compound COC(=O)C1=NNC=CC=C1 YOUPYQXYULGKCB-UHFFFAOYSA-N 0.000 description 2
KKUKTXOBAWVSHC-UHFFFAOYSA-N Dimethylphosphate Chemical compound COP(O)(=O)OC KKUKTXOBAWVSHC-UHFFFAOYSA-N 0.000 description 2
IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
206010021118 Hypotonia Diseases 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
241000907681 Morpho Species 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
HXIWFMKFZCWXKD-UHFFFAOYSA-N OC(=O)C1=CNC=CC=N1 Chemical compound OC(=O)C1=CNC=CC=N1 HXIWFMKFZCWXKD-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
238000006972 Polonovski rearrangement reaction Methods 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
241000384512 Trachichthyidae Species 0.000 description 2
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000004103 aminoalkyl group Chemical group 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
150000001557 benzodiazepines Chemical class 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 2
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000006837 decompression Effects 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
238000006297 dehydration reaction Methods 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
238000010828 elution Methods 0.000 description 2
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 2
239000011521 glass Substances 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
229910000039 hydrogen halide Inorganic materials 0.000 description 2
239000012433 hydrogen halide Substances 0.000 description 2
AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 2
150000002466 imines Chemical class 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
125000002346 iodo group Chemical group I* 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
239000011968 lewis acid catalyst Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
HQILEKXOLSEGRB-UHFFFAOYSA-N methyl 2-(diazepin-1-yl)acetate Chemical compound COC(=O)CN1C=CC=CC=N1 HQILEKXOLSEGRB-UHFFFAOYSA-N 0.000 description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
239000013081 microcrystal Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
230000036640 muscle relaxation Effects 0.000 description 2
AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 description 2
229910052759 nickel Inorganic materials 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
150000004967 organic peroxy acids Chemical class 0.000 description 2
GSWAOPJLTADLTN-UHFFFAOYSA-N oxidanimine Chemical compound [O-][NH3+] GSWAOPJLTADLTN-UHFFFAOYSA-N 0.000 description 2
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 2
125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
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 2
239000000376 reactant Substances 0.000 description 2
230000008707 rearrangement Effects 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
UMFCIIBZHQXRCJ-NSCUHMNNSA-N trans-anol Chemical compound C\C=C\C1=CC=C(O)C=C1 UMFCIIBZHQXRCJ-NSCUHMNNSA-N 0.000 description 2
238000005866 tritylation reaction Methods 0.000 description 2
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 2
238000010792 warming Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 1
ROLLNLXXOVULIM-UHFFFAOYSA-N 1,2-dihydrodiazepin-3-one Chemical compound O=C1NNC=CC=C1 ROLLNLXXOVULIM-UHFFFAOYSA-N 0.000 description 1
KQDNSEFPLFIZBE-UHFFFAOYSA-N 1H-1,2-benzodiazepine-3-carbohydrazide Chemical compound NNC(=O)C1=NNc2ccccc2C=C1 KQDNSEFPLFIZBE-UHFFFAOYSA-N 0.000 description 1
XDSFEVFCNJALNV-BTJKTKAUSA-N 1h-1,2-benzodiazepine;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.N1N=CC=CC2=CC=CC=C12 XDSFEVFCNJALNV-BTJKTKAUSA-N 0.000 description 1
VFQUUHHGXKJAKD-UHFFFAOYSA-N 2-(diazepin-1-yl)acetic acid Chemical compound OC(=O)CN1C=CC=CC=N1 VFQUUHHGXKJAKD-UHFFFAOYSA-N 0.000 description 1
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-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
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
RIGSDAIXRQTHFQ-UHFFFAOYSA-N 4-[[5-(2-chlorophenyl)-7-nitro-3h-1,4-benzodiazepin-2-yl]oxy-morpholin-4-ylphosphoryl]morpholine Chemical compound C12=CC([N+](=O)[O-])=CC=C2N=C(OP(=O)(N2CCOCC2)N2CCOCC2)CN=C1C1=CC=CC=C1Cl RIGSDAIXRQTHFQ-UHFFFAOYSA-N 0.000 description 1
QJCJVSPJCMFXKS-UHFFFAOYSA-N 4-[[7-chloro-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-yl]oxy-morpholin-4-ylphosphoryl]morpholine Chemical compound FC1=CC=CC=C1C1=NCC(OP(=O)(N2CCOCC2)N2CCOCC2)=NC2=CC=C(Cl)C=C12 QJCJVSPJCMFXKS-UHFFFAOYSA-N 0.000 description 1
MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
CWARBGBMVWXZNY-UHFFFAOYSA-N 5-(2-chlorophenyl)-7-nitro-n-(nitrosomethyl)-3h-1,4-benzodiazepin-2-amine Chemical compound C12=CC([N+](=O)[O-])=CC=C2N=C(NCN=O)CN=C1C1=CC=CC=C1Cl CWARBGBMVWXZNY-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
XBWAZCLHZCFCGK-UHFFFAOYSA-N 7-chloro-1-methyl-5-phenyl-3,4-dihydro-2h-1,4-benzodiazepin-1-ium;chloride Chemical compound [Cl-].C12=CC(Cl)=CC=C2[NH+](C)CCN=C1C1=CC=CC=C1 XBWAZCLHZCFCGK-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
PRVLPKDVTIWRIX-UHFFFAOYSA-N 8-chloro-1-methyl-6-phenyl-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC(C(N)=O)=C2CN=C1C1=CC=CC=C1 PRVLPKDVTIWRIX-UHFFFAOYSA-N 0.000 description 1
SNNAXVYUFKNABL-UHFFFAOYSA-N 8-chloro-6-(2-fluorophenyl)-4h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound FC1=CC=CC=C1C1=NCC2=CN=CN2C2=CC=C(Cl)C=C12 SNNAXVYUFKNABL-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
244000144730 Amygdalus persica Species 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
239000005973 Carvone Substances 0.000 description 1
ZHLUNLFRDZLRJB-UHFFFAOYSA-N ClOC.[Na] Chemical compound ClOC.[Na] ZHLUNLFRDZLRJB-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-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
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 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
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
240000006240 Linum usitatissimum Species 0.000 description 1
235000004431 Linum usitatissimum Nutrition 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
241000556720 Manga Species 0.000 description 1
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
241001024304 Mino Species 0.000 description 1
241001072332 Monia Species 0.000 description 1
150000004008 N-nitroso compounds Chemical class 0.000 description 1
PZQFZFREKLYPOJ-UHFFFAOYSA-N N1C=C(N=CC=C1)C(=O)N Chemical compound N1C=C(N=CC=C1)C(=O)N PZQFZFREKLYPOJ-UHFFFAOYSA-N 0.000 description 1
JQBJBWWVSKXWSB-UHFFFAOYSA-N N1C=CN=CC=C1CC(=O)O Chemical compound N1C=CN=CC=C1CC(=O)O JQBJBWWVSKXWSB-UHFFFAOYSA-N 0.000 description 1
229910021586 Nickel(II) chloride Inorganic materials 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
241000233855 Orchidaceae Species 0.000 description 1
241000237502 Ostreidae Species 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
235000006040 Prunus persica var persica Nutrition 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
206010039897 Sedation Diseases 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
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
108010021119 Trichosanthin Proteins 0.000 description 1
241000863032 Trieres Species 0.000 description 1
244000176261 Viburnum cassinoides Species 0.000 description 1
KVKLTYSBPAIVOC-UHFFFAOYSA-N [8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepin-3-yl]methanol Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC(CO)=C2CN=C1C1=CC=CC=C1F KVKLTYSBPAIVOC-UHFFFAOYSA-N 0.000 description 1
POYZUGGDLGLXCC-UHFFFAOYSA-I [Cl-].[Li+].[Li+].[Li+].[Li+].[Li+].[Cl-].[Cl-].[Cl-].[Cl-] Chemical compound [Cl-].[Li+].[Li+].[Li+].[Li+].[Li+].[Cl-].[Cl-].[Cl-].[Cl-] POYZUGGDLGLXCC-UHFFFAOYSA-I 0.000 description 1
NJVHJTQSGGRHGP-UHFFFAOYSA-K [Li].[Al+3].[Cl-].[Cl-].[Cl-] Chemical compound [Li].[Al+3].[Cl-].[Cl-].[Cl-] NJVHJTQSGGRHGP-UHFFFAOYSA-K 0.000 description 1
DSGABDNOPMWXIG-UHFFFAOYSA-M [Na+].[Cl-].CN(C)C=O Chemical compound [Na+].[Cl-].CN(C)C=O DSGABDNOPMWXIG-UHFFFAOYSA-M 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
125000000033 alkoxyamino group Chemical group 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
XDNOAQHAHHYQLB-UHFFFAOYSA-N aminomethyl 2-[7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-ylidene]acetate Chemical compound C12=CC(Cl)=CC=C2NC(=CC(=O)OCN)CN=C1C1=CC=CC=C1Cl XDNOAQHAHHYQLB-UHFFFAOYSA-N 0.000 description 1
150000008064 anhydrides Chemical class 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
239000003125 aqueous solvent Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
239000012455 biphasic mixture Substances 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
229940045348 brown mixture Drugs 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
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000001669 calcium Chemical class 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
FCVCYPORNYEAAV-UHFFFAOYSA-N chloromethane;hydrochloride Chemical compound Cl.ClC FCVCYPORNYEAAV-UHFFFAOYSA-N 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
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
238000006482 condensation reaction Methods 0.000 description 1
239000010949 copper Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
125000004966 cyanoalkyl group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
239000002037 dichloromethane fraction Substances 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002168 ethanoic acid esters Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000004744 fabric Substances 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
125000001153 fluoro group Chemical class F* 0.000 description 1
QEWYKACRFQMRMB-UHFFFAOYSA-M fluoroacetate Chemical compound [O-]C(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-M 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000004927 fusion Effects 0.000 description 1
208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
GTDCHGNGVGRHQY-UHFFFAOYSA-N hexoprenaline sulfate Chemical compound [O-]S([O-])(=O)=O.C=1C=C(O)C(O)=CC=1C(O)C[NH2+]CCCCCC[NH2+]CC(O)C1=CC=C(O)C(O)=C1 GTDCHGNGVGRHQY-UHFFFAOYSA-N 0.000 description 1
238000011905 homologation Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
HSSFHZJIMRUXDM-UHFFFAOYSA-N hydroxy(oxo)azanium chloride Chemical compound Cl.[O-][NH+]=O HSSFHZJIMRUXDM-UHFFFAOYSA-N 0.000 description 1
KLNFAMGHSZQYHR-UHFFFAOYSA-N imidazo[4,5-i][1,2]benzodiazepine Chemical compound C1=CC=NN=C2C3=NC=NC3=CC=C21 KLNFAMGHSZQYHR-UHFFFAOYSA-N 0.000 description 1
238000007654 immersion Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
229910052748 manganese Inorganic materials 0.000 description 1
239000011572 manganese Substances 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
OLLFATJQDVODBO-UHFFFAOYSA-N methyl 2-[7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-ylidene]acetate Chemical compound C12=CC(Cl)=CC=C2NC(=CC(=O)OC)CN=C1C1=CC=CC=C1Cl OLLFATJQDVODBO-UHFFFAOYSA-N 0.000 description 1
RYYIITJZACXMQL-UHFFFAOYSA-N methyl 2-[7-chloro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2-yl]-2-hydroxyiminoacetate Chemical compound COC(C(C1=NC2=C(C(=NC1)C1=C(C=CC=C1)F)C=C(C=C2)Cl)=NO)=O RYYIITJZACXMQL-UHFFFAOYSA-N 0.000 description 1
BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical compound CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 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
ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
229940035363 muscle relaxants Drugs 0.000 description 1
239000003158 myorelaxant agent Substances 0.000 description 1
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
CLOCFUZWZQDXQH-UHFFFAOYSA-N n-(nitrosomethyl)-5-phenyl-3h-1,4-benzodiazepin-2-amine Chemical compound N=1CC(NCN=O)=NC2=CC=CC=C2C=1C1=CC=CC=C1 CLOCFUZWZQDXQH-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
235000020636 oyster Nutrition 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
229940100595 phenylacetaldehyde Drugs 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
CPGRMGOILBSUQC-UHFFFAOYSA-N phosphoryl azide Chemical compound [N-]=[N+]=NP(=O)(N=[N+]=[N-])N=[N+]=[N-] CPGRMGOILBSUQC-UHFFFAOYSA-N 0.000 description 1
230000000865 phosphorylative effect Effects 0.000 description 1
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
229940072033 potash Drugs 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000012545 processing Methods 0.000 description 1
CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000036280 sedation Effects 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
238000005245 sintering Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000004575 stone Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
150000003511 tertiary amides Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
229940125725 tranquilizer Drugs 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

JP51073932A 1975-08-07 1976-06-24 Compound and production thereof Granted JPS5219697A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US60269175A	1975-08-07	1975-08-07
US66366076A	1976-03-04	1976-03-04

Publications (2)

Publication Number	Publication Date
JPS5219697A JPS5219697A (en)	1977-02-15
JPS6249273B2 true JPS6249273B2 (hu)	1987-10-19

Family

ID=27084218

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP51073932A Granted JPS5219697A (en)	1975-08-07	1976-06-24	Compound and production thereof

Country Status (21)

Country	Link
JP (1)	JPS5219697A (hu)
AR (2)	AR218433A1 (hu)
BR (1)	BR7604545A (hu)
DD (1)	DD126642A5 (hu)
DK (1)	DK162495C (hu)
ES (4)	ES446261A1 (hu)
FI (1)	FI63405C (hu)
GR (1)	GR58471B (hu)
HK (1)	HK63481A (hu)
HU (2)	HU181885B (hu)
IE (1)	IE43762B1 (hu)
IL (3)	IL49161A (hu)
KE (1)	KE3174A (hu)
MY (1)	MY8200215A (hu)
NO (3)	NO148814C (hu)
NZ (1)	NZ180218A (hu)
PH (1)	PH16624A (hu)
PL (2)	PL106837B1 (hu)
PT (1)	PT64882B (hu)
SU (2)	SU730308A3 (hu)
YU (1)	YU42801B (hu)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4118386A (en) *	1977-04-04	1978-10-03	Hoffmann-La Roche Inc.	Synthesis of imidazo[1,5-a]diazepine-3-carboxylates
JPS60178016U (ja) *	1984-05-01	1985-11-26	住友ゴム工業株式会社	車止め部材
WO2006045429A1 (en) *	2004-10-20	2006-05-04	F. Hoffmann-La Roche Ag	Halogen substituted benzodiazepine derivatives

1976
- 1976-03-05 IL IL49161A patent/IL49161A/xx unknown
- 1976-03-05 NZ NZ18021876A patent/NZ180218A/xx unknown
- 1976-03-06 GR GR50260A patent/GR58471B/el unknown
- 1976-03-08 NO NO760798A patent/NO148814C/no unknown
- 1976-03-08 FI FI760589A patent/FI63405C/fi not_active IP Right Cessation
- 1976-03-08 IE IE47076A patent/IE43762B1/en unknown
- 1976-03-09 DK DK101176A patent/DK162495C/da not_active IP Right Cessation
- 1976-03-09 PT PT6488276A patent/PT64882B/pt unknown
- 1976-03-09 ES ES446261A patent/ES446261A1/es not_active Expired
- 1976-03-09 SU SU762328361A patent/SU730308A3/ru active
- 1976-05-20 DD DD19294376A patent/DD126642A5/xx unknown
- 1976-06-03 AR AR26350476A patent/AR218433A1/es active
- 1976-06-04 HU HUHO001910 patent/HU181885B/hu unknown
- 1976-06-04 HU HUHO000014 patent/HU189631B/hu unknown
- 1976-06-24 JP JP51073932A patent/JPS5219697A/ja active Granted
- 1976-07-12 BR BR7604545A patent/BR7604545A/pt unknown
- 1976-08-04 PL PL20751076A patent/PL106837B1/pl unknown
- 1976-08-04 PL PL19162076A patent/PL106252B1/pl unknown
- 1976-08-06 PH PH18771A patent/PH16624A/en unknown
1977
- 1977-03-17 SU SU772461008A patent/SU725563A3/ru active
- 1977-03-28 AR AR26700977A patent/AR215887A1/es active
- 1977-10-01 ES ES462844A patent/ES462844A1/es not_active Expired
- 1977-10-01 ES ES462843A patent/ES462843A1/es not_active Expired
- 1977-10-01 ES ES462846A patent/ES462846A1/es not_active Expired
1979
- 1979-01-11 IL IL56415A patent/IL56415A0/xx unknown
- 1979-01-11 IL IL56414A patent/IL56414A0/xx unknown
1980
- 1980-09-08 NO NO802651A patent/NO149136C/no unknown
- 1980-09-08 NO NO802652A patent/NO149137C/no unknown
1981
- 1981-11-24 KE KE317481A patent/KE3174A/xx unknown
- 1981-12-17 HK HK63481A patent/HK63481A/xx unknown
1982
- 1982-09-28 YU YU218082A patent/YU42801B/xx unknown
- 1982-12-30 MY MY8200215A patent/MY8200215A/xx unknown

Also Published As

Publication number	Publication date
DK101176A (da)	1977-02-08
AR218433A1 (es)	1980-06-13
PT64882A (pt)	1976-04-01
PL106837B1 (pl)	1980-01-31
NO802652L (no)	1977-02-08
FI760589A (hu)	1977-02-08
NO149137B (no)	1983-11-14
YU218082A (en)	1983-12-31
NO149137C (no)	1984-02-29
DK162495B (da)	1991-11-04
ES462844A1 (es)	1978-12-16
PL106252B1 (pl)	1979-12-31
ES446261A1 (es)	1977-12-16
ES462846A1 (es)	1978-12-16
NO760798L (hu)	1977-02-08
HU189631B (en)	1986-07-28
NZ180218A (en)	1983-07-15
JPS5219697A (en)	1977-02-15
YU42801B (en)	1988-12-31
HK63481A (en)	1981-12-24
KE3174A (en)	1982-01-08
NO149136B (no)	1983-11-14
AR215887A1 (es)	1979-11-15
IE43762B1 (en)	1981-05-20
IL49161A (en)	1982-04-30
FI63405C (fi)	1983-06-10
NO802651L (no)	1977-02-08
DK162495C (da)	1992-03-30
SU725563A3 (ru)	1980-03-30
PH16624A (en)	1983-11-28
PT64882B (fr)	1978-11-06
NO148814B (no)	1983-09-12
SU730308A3 (ru)	1980-04-25
HU181885B (en)	1983-11-28
IL56415A0 (en)	1979-03-12
DD126642A5 (hu)	1977-08-03
MY8200215A (en)	1982-12-31
FI63405B (fi)	1983-02-28
NO148814C (no)	1983-12-21
BR7604545A (pt)	1977-08-02
NO149136C (no)	1984-02-29
IE43762L (en)	1977-02-07
IL56414A0 (en)	1979-03-12
ES462843A1 (es)	1978-12-16
GR58471B (en)	1977-10-14
IL49161A0 (en)	1976-07-30

Publication	Publication Date	Title
US4280957A (en)	1981-07-28	Imidazodiazepines and processes therefor
EP0672666B1 (de)	2001-07-25	Imidazodiazepine
CA1076572A (en)	1980-04-29	Diazepine derivatives
DE2540522A1 (de)	1976-04-08	Diazepin-derivate
NO126325B (hu)	1973-01-22
US4401597A (en)	1983-08-30	Imidazodiazepines and processes therefor
US4440685A (en)	1984-04-03	Imidazodiazepines and processes therefor
JPS6249273B2 (hu)	1987-10-19
US4307237A (en)	1981-12-22	Imidazoles
US4347364A (en)	1982-08-31	Imidazodiazepines
US4347365A (en)	1982-08-31	Imidazodiazepines
US3523947A (en)	1970-08-11	1-cyclic amidine-5-aryl-1,4-benzodiazepine and process
JPS6137249B2 (hu)	1986-08-22
US4377523A (en)	1983-03-22	Imidazodiazepines and processes therefor
US3513158A (en)	1970-05-19	Process for preparing 5-aryl benzodiazepines and intermediates
US4349477A (en)	1982-09-14	Process for producing imidazodiazepines
US4368157A (en)	1983-01-11	Intermediates to produce imidazodiazepines
US4368159A (en)	1983-01-11	Intermediates to produce imidazodiazepines
US4349475A (en)	1982-09-14	Process for producing imidazodiazepines
US4368158A (en)	1983-01-11	Intermediates to produce imidazodiazepines
JPS5839682A (ja)	1983-03-08	ベンズアゼピン類
US4376074A (en)	1983-03-08	Imidazodiazepines and processes therefor
US4376075A (en)	1983-03-08	Process for producing imidazodiazepines
US4349476A (en)	1982-09-14	Process for producing imidazodiazepines
US4371468A (en)	1983-02-01	Intermediates to produce imidazodiazepines