CH511863A - Verfahren zur Herstellung von 2,4-Benzdiazepinen - Google Patents
Verfahren zur Herstellung von 2,4-BenzdiazepinenInfo
- Publication number
- CH511863A CH511863A CH435768A CH435768A CH511863A CH 511863 A CH511863 A CH 511863A CH 435768 A CH435768 A CH 435768A CH 435768 A CH435768 A CH 435768A CH 511863 A CH511863 A CH 511863A
- Authority
- CH
- Switzerland
- Prior art keywords
- radical
- lower alkyl
- group
- formula
- solution
- Prior art date
Links
- 230000002192 coccidiostatic effect Effects 0.000 title description 3
- SEADJJCWSPCSHY-UHFFFAOYSA-N 2h-2,4-benzodiazepine Chemical class N1C=NC=C2C=CC=CC2=C1 SEADJJCWSPCSHY-UHFFFAOYSA-N 0.000 title description 2
- 239000002269 analeptic agent Substances 0.000 title description 2
- 230000000694 effects Effects 0.000 title description 2
- -1 araliphatic Chemical group 0.000 claims abstract description 100
- 125000003118 aryl group Chemical group 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 239000002253 acid Substances 0.000 claims abstract description 19
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 88
- 239000000243 solution Substances 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 150000001875 compounds Chemical class 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 42
- 239000000155 melt Substances 0.000 claims description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 239000002244 precipitate Substances 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 17
- GKXVJHDEWHKBFH-UHFFFAOYSA-N [2-(aminomethyl)phenyl]methanamine Chemical compound NCC1=CC=CC=C1CN GKXVJHDEWHKBFH-UHFFFAOYSA-N 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 239000007858 starting material Substances 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000012047 saturated solution Substances 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- 241000786363 Rhampholeon spectrum Species 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 150000001409 amidines Chemical class 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000012044 organic layer Substances 0.000 claims description 4
- 150000002905 orthoesters Chemical class 0.000 claims description 4
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 4
- GLBQVJGBPFPMMV-UHFFFAOYSA-N sulfilimine Chemical compound S=N GLBQVJGBPFPMMV-UHFFFAOYSA-N 0.000 claims description 4
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 claims description 4
- TVEMVWLLFCIPJB-UHFFFAOYSA-N 2,5-dihydro-1h-2,4-benzodiazepine Chemical class C1NC=NCC2=CC=CC=C12 TVEMVWLLFCIPJB-UHFFFAOYSA-N 0.000 claims description 3
- ABKWMWRLTXPAOG-UHFFFAOYSA-N 3-methyl-2,5-dihydro-1H-2,4-benzodiazepine hydrochloride Chemical compound Cl.CC=1NCC2=C(CN1)C=CC=C2 ABKWMWRLTXPAOG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical class C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 claims description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 229910021529 ammonia Inorganic materials 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
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- AINBZKYUNWUTRE-UHFFFAOYSA-N ethanol;propan-2-ol Chemical compound CCO.CC(C)O AINBZKYUNWUTRE-UHFFFAOYSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- 239000011976 maleic acid Substances 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000001302 tertiary amino group Chemical group 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- XFKIAWAJJMTZST-UHFFFAOYSA-N 3-benzyl-2,5-dihydro-1H-2,4-benzodiazepine hydrochloride Chemical compound Cl.C(C1=CC=CC=C1)C=1NCC2=C(CN1)C=CC=C2 XFKIAWAJJMTZST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- YATORDWKULMECZ-UHFFFAOYSA-N C(C=C/C(=O)O)(=O)O.C1(=CC=CC=C1)C=1NCC2=C(CN1)C=CC=C2 Chemical compound C(C=C/C(=O)O)(=O)O.C1(=CC=CC=C1)C=1NCC2=C(CN1)C=CC=C2 YATORDWKULMECZ-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- FPWNQPQTICPCOM-UHFFFAOYSA-N acetonitrile;propan-2-ol Chemical compound CC#N.CC(C)O FPWNQPQTICPCOM-UHFFFAOYSA-N 0.000 claims description 2
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 2
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 3
- DQPXYXMPFYMSQW-UHFFFAOYSA-N N-methyl-1,2,4,5-tetrahydro-2,4-benzodiazepin-3-imine Chemical compound CNC=1NCC2=C(CN1)C=CC=C2 DQPXYXMPFYMSQW-UHFFFAOYSA-N 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 abstract description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract 3
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 abstract 1
- 150000001204 N-oxides Chemical class 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 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 5
- 125000001424 substituent group Chemical group 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- 229910021607 Silver chloride Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- LWTMGTDJELUIOJ-UHFFFAOYSA-N 2,5-dihydro-1H-2,4-benzodiazepin-3-amine hydrochloride Chemical compound Cl.NC=1NCC2=C(CN1)C=CC=C2 LWTMGTDJELUIOJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VDEOIFDDSWXYDA-UHFFFAOYSA-N [2-(azaniumylmethyl)phenyl]methylazanium;dichloride Chemical compound Cl.Cl.NCC1=CC=CC=C1CN VDEOIFDDSWXYDA-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- ZHGASCUQXLPSDT-UHFFFAOYSA-N cyclohexanesulfonic acid Chemical compound OS(=O)(=O)C1CCCCC1 ZHGASCUQXLPSDT-UHFFFAOYSA-N 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- HBOBUTXJMIXYPE-UHFFFAOYSA-N 1,2-bis(chloromethyl)-4,5-dimethoxybenzene Chemical compound COC1=CC(CCl)=C(CCl)C=C1OC HBOBUTXJMIXYPE-UHFFFAOYSA-N 0.000 description 2
- WAYCPTONHUPFFR-UHFFFAOYSA-N 1,3-dicyclopropylthiourea Chemical compound C1CC1NC(=S)NC1CC1 WAYCPTONHUPFFR-UHFFFAOYSA-N 0.000 description 2
- AAPLVOHVDTXKEZ-UHFFFAOYSA-N 1h-2,4-benzodiazepine Chemical compound C1N=CN=CC2=CC=CC=C12 AAPLVOHVDTXKEZ-UHFFFAOYSA-N 0.000 description 2
- QWFVUWYFEIHZTO-UHFFFAOYSA-N 2-[[2-[(1,3-dioxoisoindol-2-yl)methyl]phenyl]methyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1=CC=CC=C1CN1C(=O)C2=CC=CC=C2C1=O QWFVUWYFEIHZTO-UHFFFAOYSA-N 0.000 description 2
- ZXIMTZPOPPEWHU-UHFFFAOYSA-N 4,5-dimethoxy-3h-2-benzofuran-1-one Chemical compound COC1=CC=C2C(=O)OCC2=C1OC ZXIMTZPOPPEWHU-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- CTFSJPICTMBTJD-UHFFFAOYSA-N Cl.C1(=CC=CC=C1)C=1NCC2=C(CN1)C=CC=C2 Chemical compound Cl.C1(=CC=CC=C1)C=1NCC2=C(CN1)C=CC=C2 CTFSJPICTMBTJD-UHFFFAOYSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FADGZQFGPHEKLU-UHFFFAOYSA-N [2-(hydroxymethyl)-4,5-dimethoxyphenyl]methanol Chemical compound COC1=CC(CO)=C(CO)C=C1OC FADGZQFGPHEKLU-UHFFFAOYSA-N 0.000 description 2
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003460 sulfonic acids Chemical class 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- KNXVOGGZOFOROK-UHFFFAOYSA-N trimagnesium;dioxido(oxo)silane;hydroxy-oxido-oxosilane Chemical compound [Mg+2].[Mg+2].[Mg+2].O[Si]([O-])=O.O[Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O KNXVOGGZOFOROK-UHFFFAOYSA-N 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- KQMBNFRGIJUXOT-UHFFFAOYSA-N 1,2,4,5-tetrahydro-2,4-benzodiazepin-3-one Chemical compound C1NC(=O)NCC2=CC=CC=C21 KQMBNFRGIJUXOT-UHFFFAOYSA-N 0.000 description 1
- VZHMHRSXWGQNFT-UHFFFAOYSA-N 1,2,4,5-tetrahydro-2,4-benzodiazepine-3-thione Chemical compound C1NC(=S)NCC2=CC=CC=C21 VZHMHRSXWGQNFT-UHFFFAOYSA-N 0.000 description 1
- KGKAYWMGPDWLQZ-UHFFFAOYSA-N 1,2-bis(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1CBr KGKAYWMGPDWLQZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- C07D243/04—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63049767A | 1967-04-13 | 1967-04-13 | |
| US69442167A | 1967-12-29 | 1967-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH511863A true CH511863A (de) | 1971-08-31 |
Family
ID=27091165
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH435768A CH511863A (de) | 1967-04-13 | 1968-03-25 | Verfahren zur Herstellung von 2,4-Benzdiazepinen |
| CH258071A CH527828A (de) | 1967-04-13 | 1968-03-25 | Verfahren zur Herstellung von 2,4-Benzdiazepinen |
| CH257971A CH523264A (de) | 1967-04-13 | 1968-03-25 | Verfahren zur Herstellung von 2,4 Benzdiazepinen |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH258071A CH527828A (de) | 1967-04-13 | 1968-03-25 | Verfahren zur Herstellung von 2,4-Benzdiazepinen |
| CH257971A CH523264A (de) | 1967-04-13 | 1968-03-25 | Verfahren zur Herstellung von 2,4 Benzdiazepinen |
Country Status (5)
| Country | Link |
|---|---|
| BE (1) | BE713698A (Direct) |
| CH (3) | CH511863A (Direct) |
| DE (1) | DE1770135A1 (Direct) |
| FR (2) | FR1588463A (Direct) |
| GB (1) | GB1183135A (Direct) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007050721A2 (en) | 2005-10-27 | 2007-05-03 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW245719B (Direct) * | 1990-09-10 | 1995-04-21 | Sterling Winthrop Inc | |
| US5380721A (en) * | 1990-09-10 | 1995-01-10 | Sterling Winthrop Inc. | Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents |
| CA2104060A1 (en) * | 1992-11-10 | 1994-05-11 | Robert Ed Johnson | Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents |
| GB9425701D0 (en) * | 1994-12-20 | 1995-02-22 | Wellcome Found | Enzyme inhibitors |
| WO2005058311A1 (en) * | 2003-12-15 | 2005-06-30 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
-
1968
- 1968-03-25 CH CH435768A patent/CH511863A/de not_active IP Right Cessation
- 1968-03-25 CH CH258071A patent/CH527828A/de not_active IP Right Cessation
- 1968-03-25 CH CH257971A patent/CH523264A/de not_active IP Right Cessation
- 1968-04-05 DE DE19681770135 patent/DE1770135A1/de active Pending
- 1968-04-09 GB GB1694368A patent/GB1183135A/en not_active Expired
- 1968-04-11 FR FR1588463D patent/FR1588463A/fr not_active Expired
- 1968-04-12 BE BE713698D patent/BE713698A/xx unknown
- 1968-07-02 FR FR157515A patent/FR7495M/fr not_active Expired
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007050721A2 (en) | 2005-10-27 | 2007-05-03 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| WO2007050721A3 (en) * | 2005-10-27 | 2007-06-14 | Schering Corp | Heterocyclic aspartyl protease inhibitors |
| US7763606B2 (en) | 2005-10-27 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US8202854B2 (en) | 2005-10-27 | 2012-06-19 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| FR1588463A (Direct) | 1970-04-17 |
| DE1770135A1 (de) | 1971-09-23 |
| BE713698A (Direct) | 1968-10-14 |
| CH527828A (de) | 1972-09-15 |
| CH523264A (de) | 1972-05-31 |
| GB1183135A (en) | 1970-03-04 |
| FR7495M (Direct) | 1969-12-08 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |