FI68832C - Foerfarande foer framstaellning av terapeutiskt anvaendbara pyimido(5,4-d)(2)bensazepiner - Google Patents
Foerfarande foer framstaellning av terapeutiskt anvaendbara pyimido(5,4-d)(2)bensazepiner Download PDFInfo
- Publication number
- FI68832C FI68832C FI800367A FI800367A FI68832C FI 68832 C FI68832 C FI 68832C FI 800367 A FI800367 A FI 800367A FI 800367 A FI800367 A FI 800367A FI 68832 C FI68832 C FI 68832C
- Authority
- FI
- Finland
- Prior art keywords
- compound
- chloro
- mixture
- ether
- methylene chloride
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical group 0.000 claims abstract description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000460 chlorine Substances 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 62
- 238000000034 method Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- 150000008038 benzoazepines Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- -1 alpha -hydroxy ethyl Chemical group 0.000 abstract description 35
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 239000002249 anxiolytic agent Substances 0.000 abstract description 3
- SYYWEHJLUMPGIZ-UHFFFAOYSA-N C1=CC=NC=C2C3=CNC=NC3=CC=C21 Chemical class C1=CC=NC=C2C3=CNC=NC3=CC=C21 SYYWEHJLUMPGIZ-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000949 anxiolytic effect Effects 0.000 abstract description 2
- 229940005530 anxiolytics Drugs 0.000 abstract description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 2
- 239000000932 sedative agent Substances 0.000 abstract description 2
- 229940125723 sedative agent Drugs 0.000 abstract description 2
- 150000002431 hydrogen Chemical class 0.000 abstract 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 abstract 1
- 125000004423 acyloxy group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 125000003396 thiol group Chemical class [H]S* 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 348
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 157
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 78
- 239000000243 solution Substances 0.000 description 77
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 25
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 239000012467 final product Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000000908 ammonium hydroxide Substances 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 8
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- GZCIHDWNYQTGOU-UHFFFAOYSA-N 2h-1-benzazepine Chemical compound C1C=CC=C2C=CC=CC2=N1 GZCIHDWNYQTGOU-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 6
- 150000001409 amidines Chemical class 0.000 description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 5
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- QXUNLRUYUXSFQE-UHFFFAOYSA-N 1h-1-benzazepin-2-amine Chemical compound N1C(N)=CC=CC2=CC=CC=C21 QXUNLRUYUXSFQE-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 150000002357 guanidines Chemical class 0.000 description 4
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- KKGYBQFRHIXAMA-UHFFFAOYSA-N 8-chloro-1-(2-chlorophenyl)-4-(dimethylaminomethylidene)-2-oxido-3h-2-benzazepin-2-ium-5-one Chemical compound C12=CC(Cl)=CC=C2C(=O)C(=CN(C)C)C[N+]([O-])=C1C1=CC=CC=C1Cl KKGYBQFRHIXAMA-UHFFFAOYSA-N 0.000 description 3
- XTRICTUJBXEEFH-UHFFFAOYSA-N 8-chloro-4-(dimethylaminomethylidene)-1-(2-fluorophenyl)-3h-2-benzazepin-5-one Chemical compound C12=CC(Cl)=CC=C2C(=O)C(=CN(C)C)CN=C1C1=CC=CC=C1F XTRICTUJBXEEFH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000001119 stannous chloride Substances 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- XUUSYXJGMRQBKQ-UHFFFAOYSA-N 2h-2-benzazepine Chemical compound N1C=CC=C2C=CC=CC2=C1 XUUSYXJGMRQBKQ-UHFFFAOYSA-N 0.000 description 2
- JTVYVDXMCGQFQM-UHFFFAOYSA-N 8-chloro-1-(2-fluorophenyl)-2-oxido-3,4-dihydro-2-benzazepin-2-ium-5-one Chemical compound C12=CC(Cl)=CC=C2C(=O)CC[N+]([O-])=C1C1=CC=CC=C1F JTVYVDXMCGQFQM-UHFFFAOYSA-N 0.000 description 2
- MXBMBCKVMVLOBI-UHFFFAOYSA-N 8-chloro-1-(2-fluorophenyl)-3,4-dihydro-2-benzazepin-5-one Chemical compound FC1=CC=CC=C1C1=NCCC(=O)C2=CC=C(Cl)C=C12 MXBMBCKVMVLOBI-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000005457 ice water 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
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- VWXLCWNPSOUPPE-UHFFFAOYSA-N (1-amino-2-methylpropylidene)azanium;chloride Chemical compound Cl.CC(C)C(N)=N VWXLCWNPSOUPPE-UHFFFAOYSA-N 0.000 description 1
- QKHMMSDZCDDEIT-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-benzazepin-5-one Chemical compound ClC1=C(C=CC=C1)C1=NC=CC(C2=C1C=CC=C2)=O QKHMMSDZCDDEIT-UHFFFAOYSA-N 0.000 description 1
- FZKBKPDFCRYDJT-UHFFFAOYSA-N 1-(2-chlorophenyl)-4-(dimethylaminomethylidene)-3h-2-benzazepin-5-one Chemical compound C12=CC=CC=C2C(=O)C(=CN(C)C)CN=C1C1=CC=CC=C1Cl FZKBKPDFCRYDJT-UHFFFAOYSA-N 0.000 description 1
- NIAIVOLKKAOKHX-UHFFFAOYSA-N 1-oxo-3-phenylindene-2-carbonitrile Chemical compound C12=CC=CC=C2C(=O)C(C#N)=C1C1=CC=CC=C1 NIAIVOLKKAOKHX-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- GNPDWXCPMSXHJP-UHFFFAOYSA-N 1h-1-benzazepine;dihydrochloride Chemical compound Cl.Cl.N1C=CC=CC2=CC=CC=C12 GNPDWXCPMSXHJP-UHFFFAOYSA-N 0.000 description 1
- CDBDGQJXEZUYSN-UHFFFAOYSA-N 2-amino-4-(2-benzoylphenyl)pyrimidine-5-carbonitrile Chemical compound NC1=NC=C(C#N)C(C=2C(=CC=CC=2)C(=O)C=2C=CC=CC=2)=N1 CDBDGQJXEZUYSN-UHFFFAOYSA-N 0.000 description 1
- MHAJOOQWISDTQV-UHFFFAOYSA-N 2-amino-4-[4-chloro-2-(2-fluorobenzoyl)phenyl]pyrimidine-5-carbonitrile Chemical compound NC1=NC=C(C#N)C(C=2C(=CC(Cl)=CC=2)C(=O)C=2C(=CC=CC=2)F)=N1 MHAJOOQWISDTQV-UHFFFAOYSA-N 0.000 description 1
- RTHFDQMJGQMEEG-UHFFFAOYSA-N 2-benzazepin-5-one Chemical compound O=C1C=CN=CC2=CC=CC=C12 RTHFDQMJGQMEEG-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
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- MCUPNPQIJUEVRX-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-2-methyl-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=NC(C)=NC=C2CN=C1C1=CC=CC=C1Cl MCUPNPQIJUEVRX-UHFFFAOYSA-N 0.000 description 1
- DEGASONJFRAOIK-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-5h-pyrimido[5,4-d][2]benzazepin-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(N)=NC=C2CN=C1C1=CC=CC=C1Cl DEGASONJFRAOIK-UHFFFAOYSA-N 0.000 description 1
- NBDMULRONZEXNZ-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-6-oxido-5h-pyrimido[5,4-d][2]benzazepin-6-ium-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(N)=NC=C2C[N+]([O-])=C1C1=CC=CC=C1F NBDMULRONZEXNZ-UHFFFAOYSA-N 0.000 description 1
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- NQSMEZJWJJVYOI-UHFFFAOYSA-N Methyl 2-benzoylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 NQSMEZJWJJVYOI-UHFFFAOYSA-N 0.000 description 1
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- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- CMDKPGRTAQVGFQ-RMKNXTFCSA-N cinoxate Chemical compound CCOCCOC(=O)\C=C\C1=CC=C(OC)C=C1 CMDKPGRTAQVGFQ-RMKNXTFCSA-N 0.000 description 1
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- 125000001207 fluorophenyl group Chemical group 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
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000005907 ketalization reaction Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QARMKTQJNVPEBZ-UHFFFAOYSA-N methyl 2-[4-(chloromethyl)-2-phenyl-1,3-dioxolan-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C1(C=2C=CC=CC=2)OC(CCl)CO1 QARMKTQJNVPEBZ-UHFFFAOYSA-N 0.000 description 1
- WQYQQUWRQLYQOC-UHFFFAOYSA-N methyl 4-chloro-2-(2-fluorobenzoyl)benzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1F WQYQQUWRQLYQOC-UHFFFAOYSA-N 0.000 description 1
- JGOLBCMSRFUMMT-UHFFFAOYSA-N methyl 4-chloro-2-[4-(chloromethyl)-2-(2-fluorophenyl)-1,3-dioxolan-2-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1C1(C=2C(=CC=CC=2)F)OC(CCl)CO1 JGOLBCMSRFUMMT-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 description 1
- 102220074243 rs34116584 Human genes 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 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
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- LXEXBJXDGVGRAR-UHFFFAOYSA-N trichloro(trichlorosilyl)silane Chemical compound Cl[Si](Cl)(Cl)[Si](Cl)(Cl)Cl LXEXBJXDGVGRAR-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C291/00—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00
- C07C291/02—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds
- C07C291/04—Compounds containing carbon and nitrogen and having functional groups not covered by groups C07C201/00 - C07C281/00 containing nitrogen-oxide bonds containing amino-oxide bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
- C07C309/65—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms of a saturated carbon skeleton
- C07C309/66—Methanesulfonates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/34—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/16—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1011879A | 1979-02-07 | 1979-02-07 | |
| US1011879 | 1979-02-07 | ||
| US1670979A | 1979-03-01 | 1979-03-01 | |
| US1670979 | 1979-03-01 | ||
| CH51080 | 1980-01-22 | ||
| CH51080 | 1980-01-22 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI800367A7 FI800367A7 (fi) | 1980-08-08 |
| FI68832B FI68832B (fi) | 1985-07-31 |
| FI68832C true FI68832C (fi) | 1985-11-11 |
Family
ID=27172162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI800367A FI68832C (fi) | 1979-02-07 | 1980-02-06 | Foerfarande foer framstaellning av terapeutiskt anvaendbara pyimido(5,4-d)(2)bensazepiner |
Country Status (26)
| Country | Link |
|---|---|
| EP (1) | EP0014470B1 (cs) |
| AT (1) | ATE14225T1 (cs) |
| AU (1) | AU535233B2 (cs) |
| CA (1) | CA1138863A (cs) |
| DD (1) | DD149066A5 (cs) |
| DE (2) | DE3004381A1 (cs) |
| ES (1) | ES488311A0 (cs) |
| FI (1) | FI68832C (cs) |
| FR (1) | FR2450833A1 (cs) |
| GB (1) | GB2043636B (cs) |
| HU (1) | HU182662B (cs) |
| IE (1) | IE49630B1 (cs) |
| IL (1) | IL59316A (cs) |
| IN (1) | IN151574B (cs) |
| IT (1) | IT1140535B (cs) |
| LU (1) | LU82143A1 (cs) |
| MC (1) | MC1314A1 (cs) |
| MT (1) | MTP864B (cs) |
| NL (1) | NL8000715A (cs) |
| NO (1) | NO153138C (cs) |
| NZ (1) | NZ192803A (cs) |
| PT (1) | PT70794B (cs) |
| RO (1) | RO79168A (cs) |
| SE (1) | SE8000964L (cs) |
| SU (1) | SU1181547A3 (cs) |
| YU (1) | YU32380A (cs) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK347781A (da) * | 1980-08-05 | 1982-02-06 | Hoffmann La Roche | Fremgangsmaade til fremstilling af pyrimido-(4,5-d) (2)-benzezepiner eller farmaceutisk acceptable salte deraf |
| EP0273697A3 (en) * | 1986-12-30 | 1989-11-29 | Merck & Co. Inc. | 2-benzazepines with 5- and 6- membered heterocyclic rings |
| US5013333A (en) * | 1990-04-13 | 1991-05-07 | Tennant Company | Unattended air cleaning system for surface maintenance machine |
| JP5097539B2 (ja) * | 2004-05-07 | 2012-12-12 | アムジエン・インコーポレーテツド | タンパク質キナーゼ調節剤および使用方法 |
| CA2565411C (en) | 2004-05-14 | 2010-04-20 | Millennium Pharmaceuticals, Inc. | Compounds and methods for inhibiting mitotic progression |
| US7718648B2 (en) | 2006-08-09 | 2010-05-18 | Millennium Pharmaceuticals, Inc. | Pyridobenzazepine compounds and methods for inhibiting mitotic progression |
| CL2007003244A1 (es) | 2006-11-16 | 2008-04-04 | Millennium Pharm Inc | Compuestos derivados de pirimido[5,4-d][2]benzazepina; composicion farmaceutica que comprende a dicho compuesto; y uso del compuesto para el tratamiento del cancer. |
| WO2010074724A1 (en) | 2008-12-22 | 2010-07-01 | Millennium Pharmaceuticals, Inc. | Combination of aurora kinase inhibitors and anti-cd20 antibodies |
| JO3635B1 (ar) | 2009-05-18 | 2020-08-27 | Millennium Pharm Inc | مركبات صيدلانية صلبة وطرق لانتاجها |
| US8653064B2 (en) | 2010-02-19 | 2014-02-18 | Millennium Pharmaceuticals, Inc. | Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-D][2]benzazepin-2-yl]amino}-2-methoxybenzoate |
| US20130303519A1 (en) | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| JP2018524292A (ja) | 2015-07-21 | 2018-08-30 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | オーロラキナーゼインヒビターと化学療法剤の投与 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3947585A (en) * | 1974-06-03 | 1976-03-30 | Ciba-Geigy Corporation | Pyrazolobenzazepines |
-
1980
- 1980-02-05 IL IL59316A patent/IL59316A/xx unknown
- 1980-02-05 CA CA000345062A patent/CA1138863A/en not_active Expired
- 1980-02-05 NL NL8000715A patent/NL8000715A/nl not_active Application Discontinuation
- 1980-02-05 SU SU802879255A patent/SU1181547A3/ru active
- 1980-02-05 FR FR8002469A patent/FR2450833A1/fr active Granted
- 1980-02-05 NZ NZ192803A patent/NZ192803A/en unknown
- 1980-02-06 FI FI800367A patent/FI68832C/fi not_active IP Right Cessation
- 1980-02-06 EP EP80100610A patent/EP0014470B1/de not_active Expired
- 1980-02-06 AT AT80100610T patent/ATE14225T1/de not_active IP Right Cessation
- 1980-02-06 PT PT70794A patent/PT70794B/pt unknown
- 1980-02-06 MT MT864A patent/MTP864B/xx unknown
- 1980-02-06 MC MC801426A patent/MC1314A1/xx unknown
- 1980-02-06 ES ES488311A patent/ES488311A0/es active Granted
- 1980-02-06 DE DE19803004381 patent/DE3004381A1/de not_active Withdrawn
- 1980-02-06 DD DD80218921A patent/DD149066A5/de unknown
- 1980-02-06 IE IE227/80A patent/IE49630B1/en unknown
- 1980-02-06 GB GB8003910A patent/GB2043636B/en not_active Expired
- 1980-02-06 HU HU80271A patent/HU182662B/hu unknown
- 1980-02-06 AU AU55296/80A patent/AU535233B2/en not_active Ceased
- 1980-02-06 LU LU82143A patent/LU82143A1/de unknown
- 1980-02-06 IN IN138/CAL/80A patent/IN151574B/en unknown
- 1980-02-06 NO NO800316A patent/NO153138C/no unknown
- 1980-02-06 SE SE8000964A patent/SE8000964L/xx not_active Application Discontinuation
- 1980-02-06 IT IT19740/80A patent/IT1140535B/it active
- 1980-02-06 DE DE8080100610T patent/DE3070847D1/de not_active Expired
- 1980-02-07 YU YU00323/80A patent/YU32380A/xx unknown
- 1980-02-07 RO RO80100118A patent/RO79168A/ro unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE & CO. |