DD149066A5 - Benzazepin-derivate - Google Patents
Benzazepin-derivate Download PDFInfo
- Publication number
- DD149066A5 DD149066A5 DD80218921A DD21892180A DD149066A5 DD 149066 A5 DD149066 A5 DD 149066A5 DD 80218921 A DD80218921 A DD 80218921A DD 21892180 A DD21892180 A DD 21892180A DD 149066 A5 DD149066 A5 DD 149066A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- hydrogen
- compound
- group
- lower alkyl
- formula
- Prior art date
Links
- 150000008038 benzoazepines Chemical class 0.000 title abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 61
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 230000000949 anxiolytic effect Effects 0.000 claims abstract description 6
- 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 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 109
- 239000001257 hydrogen Substances 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 83
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 31
- 150000002431 hydrogen Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- -1 alkyl mercaptan Chemical compound 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- 125000002147 dimethylamino group Chemical class [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 239000000460 chlorine Chemical group 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 229910052731 fluorine Chemical group 0.000 claims description 3
- 239000011737 fluorine Chemical group 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000002249 anxiolytic agent Substances 0.000 claims description 2
- 229940005530 anxiolytics Drugs 0.000 claims description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 5
- 239000000932 sedative agent Substances 0.000 abstract description 5
- 230000001624 sedative effect Effects 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 516
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 229
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 168
- 239000000243 solution Substances 0.000 description 111
- 239000000203 mixture Substances 0.000 description 75
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 60
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
- 229910052938 sodium sulfate Inorganic materials 0.000 description 48
- 235000011152 sodium sulphate Nutrition 0.000 description 48
- 238000001953 recrystallisation Methods 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- 239000012074 organic phase Substances 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 238000001704 evaporation Methods 0.000 description 22
- 239000013078 crystal Substances 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- 230000008020 evaporation Effects 0.000 description 19
- XUUSYXJGMRQBKQ-UHFFFAOYSA-N 2h-2-benzazepine Chemical compound N1C=CC=C2C=CC=CC2=C1 XUUSYXJGMRQBKQ-UHFFFAOYSA-N 0.000 description 18
- 239000003826 tablet Substances 0.000 description 18
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 17
- 239000000908 ammonium hydroxide Substances 0.000 description 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 229960000583 acetic acid Drugs 0.000 description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 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 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 239000012071 phase Substances 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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001409 amidines Chemical class 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 5
- 238000005903 acid hydrolysis reaction Methods 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- DWDMLLDAZABVCH-UHFFFAOYSA-N C(C)(=O)OC=1C=CNC=C2C=1C=CC=C2 Chemical compound C(C)(=O)OC=1C=CNC=C2C=1C=CC=C2 DWDMLLDAZABVCH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000007865 diluting Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 150000002357 guanidines Chemical class 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- QXUNLRUYUXSFQE-UHFFFAOYSA-N 1h-1-benzazepin-2-amine Chemical compound N1C(N)=CC=CC2=CC=CC=C21 QXUNLRUYUXSFQE-UHFFFAOYSA-N 0.000 description 3
- ZEGKMPUYDXONKA-UHFFFAOYSA-N 2,9-dichloro-7-(2-fluorophenyl)-5h-pyrimido[5,4-d][2]benzazepine Chemical compound FC1=CC=CC=C1C1=NCC2=CN=C(Cl)N=C2C2=CC=C(Cl)C=C12 ZEGKMPUYDXONKA-UHFFFAOYSA-N 0.000 description 3
- 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 3
- AQNQKCGTJAKHLW-UHFFFAOYSA-N 8-chloro-1-(2-chlorophenyl)-4-(dimethylaminomethylidene)-3h-2-benzazepin-5-one Chemical compound C12=CC(Cl)=CC=C2C(=O)C(=CN(C)C)CN=C1C1=CC=CC=C1Cl AQNQKCGTJAKHLW-UHFFFAOYSA-N 0.000 description 3
- FBRAIVNJLBZIIY-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-5h-pyrimido[5,4-d][2]benzazepin-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(N)=NC=C2CN=C1C1=CC=CC=C1F FBRAIVNJLBZIIY-UHFFFAOYSA-N 0.000 description 3
- SUBFBABAYCXTSC-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-6-oxido-5h-pyrimido[5,4-d][2]benzazepin-6-ium Chemical compound C12=CC(Cl)=CC=C2C2=NC=NC=C2C[N+]([O-])=C1C1=CC=CC=C1F SUBFBABAYCXTSC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- CPYSUUSFGSKRSD-UHFFFAOYSA-N Cl.Cl.C=1NC=CC=C2C1C=CC=C2 Chemical compound Cl.Cl.C=1NC=CC=C2C1C=CC=C2 CPYSUUSFGSKRSD-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 239000000538 analytical sample Substances 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- HCPLNOPBLVVVQV-UHFFFAOYSA-N 1-[9-chloro-7-(2-chlorophenyl)-5,7-dihydropyrimido[5,4-d][2]benzazepin-6-yl]-2,2,2-trifluoroethanone Chemical compound FC(F)(F)C(=O)N1CC2=CN=CN=C2C2=CC=C(Cl)C=C2C1C1=CC=CC=C1Cl HCPLNOPBLVVVQV-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- ILHKNPWDODKTLD-UHFFFAOYSA-N 2-hydroxy-2-benzazepine Chemical compound ON1C=CC=C2C=CC=CC2=C1 ILHKNPWDODKTLD-UHFFFAOYSA-N 0.000 description 2
- LZLWYVOPSJIVIJ-UHFFFAOYSA-N 2-sulfanyl-2-benzazepine Chemical compound C=1N(C=CC=C2C=1C=CC=C2)S LZLWYVOPSJIVIJ-UHFFFAOYSA-N 0.000 description 2
- 229940105325 3-dimethylaminopropylamine Drugs 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- YPZUHOLWZJYCOS-UHFFFAOYSA-N 5H-2-benzazepin-4-amine Chemical compound C1=NC=C(CC2=C1C=CC=C2)N YPZUHOLWZJYCOS-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
- 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 2
- 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 2
- GBYJSQRDSMCCGH-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-3-oxido-5h-pyrimido[5,4-d][2]benzazepin-3-ium Chemical compound C=1[N+]([O-])=CN=C(C2=CC=C(Cl)C=C22)C=1CN=C2C1=CC=CC=C1Cl GBYJSQRDSMCCGH-UHFFFAOYSA-N 0.000 description 2
- CLYXKIKVKJZIOF-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C=1C(Cl)=CC=C(C2=NC=NC=C2CN=2)C=1C=2C1=CC=CC=C1Cl CLYXKIKVKJZIOF-UHFFFAOYSA-N 0.000 description 2
- MTKQQUYTMHOXIJ-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-6-(4-methylphenyl)sulfonyl-3-oxido-5,7-dihydropyrimido[5,4-d][2]benzazepin-3-ium Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C=2C(=CC=CC=2)Cl)C2=CC(Cl)=CC=C2C2=NC=[N+]([O-])C=C2C1 MTKQQUYTMHOXIJ-UHFFFAOYSA-N 0.000 description 2
- WMLKIRMQFYNVCP-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-6-oxido-5h-pyrimido[5,4-d][2]benzazepin-6-ium Chemical compound C12=CC(Cl)=CC=C2C2=NC=NC=C2C[N+]([O-])=C1C1=CC=CC=C1Cl WMLKIRMQFYNVCP-UHFFFAOYSA-N 0.000 description 2
- DLXPIJHVVDJDNU-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-2-methoxy-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=NC(OC)=NC=C2CN=C1C1=CC=CC=C1F DLXPIJHVVDJDNU-UHFFFAOYSA-N 0.000 description 2
- UOMNACAACGEPRY-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-5h-pyrimido[5,4-d][2]benzazepine Chemical compound FC1=CC=CC=C1C1=NCC2=CN=CN=C2C2=CC=C(Cl)C=C12 UOMNACAACGEPRY-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-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
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 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
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000002038 ethyl acetate fraction Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 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
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 description 1
- NKQMMXJNGCHMRH-UHFFFAOYSA-N 1-(2-chlorophenyl)-3,4-dihydro-2-benzazepin-5-one Chemical compound ClC1=CC=CC=C1C1=NCCC(=O)C2=CC=CC=C12 NKQMMXJNGCHMRH-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
- HUHSJYFCHKIWEE-UHFFFAOYSA-N 1-[9-chloro-7-(2-chlorophenyl)-3-oxido-5,7-dihydropyrimido[5,4-d][2]benzazepin-3-ium-6-yl]-2,2,2-trifluoroethanone Chemical compound C=1[N+]([O-])=CN=C(C2=CC=C(Cl)C=C22)C=1CN(C(=O)C(F)(F)F)C2C1=CC=CC=C1Cl HUHSJYFCHKIWEE-UHFFFAOYSA-N 0.000 description 1
- VYZLHNQFKQTCNT-UHFFFAOYSA-N 1-phenyl-3,4-dihydro-2-benzazepin-5-one Chemical compound C12=CC=CC=C2C(=O)CCN=C1C1=CC=CC=C1 VYZLHNQFKQTCNT-UHFFFAOYSA-N 0.000 description 1
- GJPUTKWVQJEZPE-UHFFFAOYSA-N 1h-azepin-2-amine Chemical compound NC1=CC=CC=CN1 GJPUTKWVQJEZPE-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- RRIQCYWETXQGAH-UHFFFAOYSA-N 2-(2-benzazepin-2-yl)acetic acid Chemical compound OC(=O)CN1C=CC=C2C=CC=CC2=C1 RRIQCYWETXQGAH-UHFFFAOYSA-N 0.000 description 1
- OQVFYJJWNPIRHC-UHFFFAOYSA-N 2-(2-fluorophenyl)-5H-pyrimido[5,4-d][2]benzazepine Chemical compound FC1=C(C=CC=C1)C=1N=CC=2CN=CC3=C(C=2N=1)C=CC=C3 OQVFYJJWNPIRHC-UHFFFAOYSA-N 0.000 description 1
- DCWHYZCVSDAFKH-UHFFFAOYSA-N 2-[9-chloro-7-(2-fluorophenyl)-5h-pyrimido[5,4-d][2]benzazepin-2-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2C2=NC(CC(=O)O)=NC=C2CN=C1C1=CC=CC=C1F DCWHYZCVSDAFKH-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
- MNGPYQKYIBUNAE-UHFFFAOYSA-N 2-amino-4-[4-chloro-2-[4-(chloromethyl)-2-(2-fluorophenyl)-1,3-dioxolan-2-yl]phenyl]pyrimidine-5-carbonitrile Chemical compound NC1=NC=C(C#N)C(C=2C(=CC(Cl)=CC=2)C2(OC(CCl)CO2)C=2C(=CC=CC=2)F)=N1 MNGPYQKYIBUNAE-UHFFFAOYSA-N 0.000 description 1
- CUJJWOUYYROEOP-UHFFFAOYSA-N 2-benzazepin-2-amine Chemical compound NN1C=CC=C2C=CC=CC2=C1 CUJJWOUYYROEOP-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
- MIJNTXRREVCHRO-UHFFFAOYSA-N 2H-2-benzazepin-5-ol Chemical compound OC1=c2ccccc2=CNC=C1 MIJNTXRREVCHRO-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- CASIQJIGAPRTOE-UHFFFAOYSA-N 4-chloro-2-(2-fluorobenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1F CASIQJIGAPRTOE-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
- QKTFJEYRMPAOJT-UHFFFAOYSA-N 7-(2-chlorophenyl)-2-methyl-5h-pyrimido[5,4-d][2]benzazepine;methanesulfonic acid Chemical compound CS(O)(=O)=O.C12=CC=CC=C2C2=NC(C)=NC=C2CN=C1C1=CC=CC=C1Cl QKTFJEYRMPAOJT-UHFFFAOYSA-N 0.000 description 1
- AVFBPRPNJXGEOS-UHFFFAOYSA-N 7-(2-fluorophenyl)-1,5-dihydropyrimido[5,4-d][2]benzazepin-2-one Chemical compound FC1=C(C=CC=C1)C1=NCC2=C(C3=C1C=CC=C3)N=C(N=C2)O AVFBPRPNJXGEOS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SCQCNKCRFIWYPF-UHFFFAOYSA-N 8-chloro-1-(2-chlorophenyl)-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=C1Cl SCQCNKCRFIWYPF-UHFFFAOYSA-N 0.000 description 1
- UHNROOUVTRJBHP-UHFFFAOYSA-N 8-chloro-1-(2-chlorophenyl)-3,4-dihydro-2-benzazepin-5-one Chemical compound C=1C(Cl)=CC=C(C(CCN=2)=O)C=1C=2C1=CC=CC=C1Cl UHNROOUVTRJBHP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GBTZWDORYJOWFT-UHFFFAOYSA-N 8-chloro-4-(dimethylaminomethylidene)-1-phenyl-3h-2-benzazepin-5-one Chemical compound C12=CC(Cl)=CC=C2C(=O)C(=CN(C)C)CN=C1C1=CC=CC=C1 GBTZWDORYJOWFT-UHFFFAOYSA-N 0.000 description 1
- TWWXLUNHZAUPLK-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-2-methyl-6,7-dihydro-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=NC(C)=NC=C2CNC1C1=CC=CC=C1Cl TWWXLUNHZAUPLK-UHFFFAOYSA-N 0.000 description 1
- PHZNVPXRSSHABA-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-2-methyl-6,7-dihydro-5h-pyrimido[5,4-d][2]benzazepine;dihydrochloride Chemical compound Cl.Cl.C12=CC(Cl)=CC=C2C2=NC(C)=NC=C2CNC1C1=CC=CC=C1Cl PHZNVPXRSSHABA-UHFFFAOYSA-N 0.000 description 1
- MRRIGJAPQBEYKH-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-2-methyl-6-oxido-5h-pyrimido[5,4-d][2]benzazepin-3-ium 3-oxide Chemical compound C1=[N+]([O-])C(C)=NC(C2=CC=C(Cl)C=C22)=C1C[N+]([O-])=C2C1=CC=CC=C1Cl MRRIGJAPQBEYKH-UHFFFAOYSA-N 0.000 description 1
- PDMAZYVUONRRQR-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-2-methylsulfanyl-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C12=CC(Cl)=CC=C2C2=NC(SC)=NC=C2CN=C1C1=CC=CC=C1Cl PDMAZYVUONRRQR-UHFFFAOYSA-N 0.000 description 1
- HNUYGAFVROYBQF-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-3-oxido-6,7-dihydro-5h-pyrimido[5,4-d][2]benzazepin-3-ium Chemical compound C=1[N+]([O-])=CN=C(C2=CC=C(Cl)C=C22)C=1CNC2C1=CC=CC=C1Cl HNUYGAFVROYBQF-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
- YEUONTMBLBKVLO-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-5h-pyrimido[5,4-d][2]benzazepin-5-ol Chemical compound C12=CC(Cl)=CC=C2C2=NC=NC=C2C(O)N=C1C1=CC=CC=C1Cl YEUONTMBLBKVLO-UHFFFAOYSA-N 0.000 description 1
- DQNMSAQIDFHJEZ-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-5h-pyrimido[5,4-d][2]benzazepine Chemical compound C=1C(Cl)=CC=C(C2=NC=NC=C2CN2)C=1C2C1=CC=CC=C1Cl DQNMSAQIDFHJEZ-UHFFFAOYSA-N 0.000 description 1
- HHIFCDLZVSFPEC-UHFFFAOYSA-N 9-chloro-7-(2-chlorophenyl)-6-(4-methylphenyl)sulfonyl-5,7-dihydropyrimido[5,4-d][2]benzazepine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C=2C(=CC=CC=2)Cl)C2=CC(Cl)=CC=C2C2=NC=NC=C2C1 HHIFCDLZVSFPEC-UHFFFAOYSA-N 0.000 description 1
- CNKQLMWVYUANEB-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-1,5-dihydropyrimido[5,4-d][2]benzazepin-2-one Chemical compound C12=CC(Cl)=CC=C2C2=NC(O)=NC=C2CN=C1C1=CC=CC=C1F CNKQLMWVYUANEB-UHFFFAOYSA-N 0.000 description 1
- ZWCDMVXBRYPESI-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-6-oxido-1,5-dihydropyrimido[5,4-d][2]benzazepin-6-ium-2-thione Chemical compound C12=CC(Cl)=CC=C2C2=NC(S)=NC=C2C[N+]([O-])=C1C1=CC=CC=C1F ZWCDMVXBRYPESI-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
- FXBGWQBBFOHQAR-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-n,n-dimethyl-5h-pyrimido[5,4-d][2]benzazepin-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(N(C)C)=NC=C2CN=C1C1=CC=CC=C1F FXBGWQBBFOHQAR-UHFFFAOYSA-N 0.000 description 1
- SMZPEZFCUDBVTA-UHFFFAOYSA-N 9-chloro-7-(2-fluorophenyl)-n-methyl-5h-pyrimido[5,4-d][2]benzazepin-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(NC)=NC=C2CN=C1C1=CC=CC=C1F SMZPEZFCUDBVTA-UHFFFAOYSA-N 0.000 description 1
- HWHLHTJZDOBGNE-UHFFFAOYSA-N 9-chloro-7-phenyl-5h-pyrimido[5,4-d][2]benzazepin-2-amine Chemical compound C12=CC(Cl)=CC=C2C2=NC(N)=NC=C2CN=C1C1=CC=CC=C1 HWHLHTJZDOBGNE-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- MKJAYTVBWDRFCJ-UHFFFAOYSA-N C=1N(C=CC=C2C=1C=CC=C2)CC(=O)N Chemical compound C=1N(C=CC=C2C=1C=CC=C2)CC(=O)N MKJAYTVBWDRFCJ-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 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
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- XYULIKIBJYNXPC-UHFFFAOYSA-N ethyl 2-[9-chloro-7-(2-fluorophenyl)-5h-pyrimido[5,4-d][2]benzazepin-2-yl]acetate Chemical compound C12=CC(Cl)=CC=C2C2=NC(CC(=O)OCC)=NC=C2CN=C1C1=CC=CC=C1F XYULIKIBJYNXPC-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000012458 free base Substances 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
- 229940028332 halog Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- KMZNMPLEANWNRZ-UHFFFAOYSA-N methyl 4-chloro-1-[4-(chloromethyl)-2-(2-fluorophenyl)-1,3-dioxolan-2-yl]cyclohexa-2,4-diene-1-carboxylate Chemical compound COC(C1(CC=C(C=C1)Cl)C1(OCC(O1)CCl)C1=C(C=CC=C1)F)=O KMZNMPLEANWNRZ-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
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 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
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 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
- 125000006239 protecting group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229940125723 sedative agent Drugs 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
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 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
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical group 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
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000009466 transformation Effects 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
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc 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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1011879A | 1979-02-07 | 1979-02-07 | |
| US1670979A | 1979-03-01 | 1979-03-01 | |
| CH51080 | 1980-01-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD149066A5 true DD149066A5 (de) | 1981-06-24 |
Family
ID=27172162
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD80218921A DD149066A5 (de) | 1979-02-07 | 1980-02-06 | Benzazepin-derivate |
Country Status (26)
| Country | Link |
|---|---|
| EP (1) | EP0014470B1 (no) |
| AT (1) | ATE14225T1 (no) |
| AU (1) | AU535233B2 (no) |
| CA (1) | CA1138863A (no) |
| DD (1) | DD149066A5 (no) |
| DE (2) | DE3070847D1 (no) |
| ES (1) | ES8101590A1 (no) |
| FI (1) | FI68832C (no) |
| FR (1) | FR2450833A1 (no) |
| GB (1) | GB2043636B (no) |
| HU (1) | HU182662B (no) |
| IE (1) | IE49630B1 (no) |
| IL (1) | IL59316A (no) |
| IN (1) | IN151574B (no) |
| IT (1) | IT1140535B (no) |
| LU (1) | LU82143A1 (no) |
| MC (1) | MC1314A1 (no) |
| MT (1) | MTP864B (no) |
| NL (1) | NL8000715A (no) |
| NO (1) | NO153138C (no) |
| NZ (1) | NZ192803A (no) |
| PT (1) | PT70794B (no) |
| RO (1) | RO79168A (no) |
| SE (1) | SE8000964L (no) |
| SU (1) | SU1181547A3 (no) |
| YU (1) | YU32380A (no) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU547557B2 (en) * | 1980-08-05 | 1985-10-24 | F. Hoffmann-La Roche & Co. | Pyrimido (4,5-d)(2)benzazepines |
| 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 |
| MXPA06012613A (es) * | 2004-05-07 | 2007-01-31 | Amgen Inc | Derivados heterociclicos nitrogenados como moduladores de proteina cinasa y uso para el tratamiento de angiogenesis y cancer. |
| EA012112B1 (ru) | 2004-05-14 | 2009-08-28 | Миллениум Фармасьютикалз, Инк. | Соединения и способы для ингибирования митотической прогрессии |
| 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 |
| CN102770024A (zh) | 2010-02-19 | 2012-11-07 | 米伦纽姆医药公司 | 4-{[9-氯-7-(2-氟-6-甲氧基苯基)-5h-嘧啶并[5,4-d][2]苯并氮杂卓-2基]氨基}-2-甲氧基苯甲酸钠的结晶形式 |
| US20130303519A1 (en) | 2012-03-20 | 2013-11-14 | Millennium Pharmaceuticals, Inc. | Methods of treating cancer using aurora kinase inhibitors |
| EP2976086B1 (en) | 2013-03-22 | 2020-10-14 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mtorc 1/2 inhibitors and selective inhibitors of aurora a kinase |
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 FR FR8002469A patent/FR2450833A1/fr active Granted
- 1980-02-05 CA CA000345062A patent/CA1138863A/en not_active Expired
- 1980-02-05 SU SU802879255A patent/SU1181547A3/ru active
- 1980-02-05 NZ NZ192803A patent/NZ192803A/en unknown
- 1980-02-05 NL NL8000715A patent/NL8000715A/nl not_active Application Discontinuation
- 1980-02-06 IE IE227/80A patent/IE49630B1/en unknown
- 1980-02-06 LU LU82143A patent/LU82143A1/de unknown
- 1980-02-06 EP EP80100610A patent/EP0014470B1/de not_active Expired
- 1980-02-06 DD DD80218921A patent/DD149066A5/de unknown
- 1980-02-06 MC MC801426A patent/MC1314A1/xx unknown
- 1980-02-06 DE DE8080100610T patent/DE3070847D1/de not_active Expired
- 1980-02-06 GB GB8003910A patent/GB2043636B/en not_active Expired
- 1980-02-06 IT IT19740/80A patent/IT1140535B/it active
- 1980-02-06 PT PT70794A patent/PT70794B/pt 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 HU HU80271A patent/HU182662B/hu unknown
- 1980-02-06 AU AU55296/80A patent/AU535233B2/en not_active Ceased
- 1980-02-06 FI FI800367A patent/FI68832C/fi not_active IP Right Cessation
- 1980-02-06 MT MT864A patent/MTP864B/xx unknown
- 1980-02-06 ES ES488311A patent/ES8101590A1/es not_active Expired
- 1980-02-06 DE DE19803004381 patent/DE3004381A1/de not_active Withdrawn
- 1980-02-06 IN IN138/CAL/80A patent/IN151574B/en unknown
- 1980-02-06 AT AT80100610T patent/ATE14225T1/de not_active IP Right Cessation
- 1980-02-07 RO RO80100118A patent/RO79168A/ro unknown
- 1980-02-07 YU YU00323/80A patent/YU32380A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0150040B1 (de) | Imidazodiazepin-Derivate | |
| DE69930328T2 (de) | Dimere Pyrrolobenzodiazepine | |
| EP0005205B1 (de) | Substituierte 5,6-Dimethylpyrrolo(2,3-d)pyrimidine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| EP0031080A1 (de) | 2-Acylaminomethyl-1,4-benzodiazepine und deren Salze sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DD149066A5 (de) | Benzazepin-derivate | |
| DD263772A5 (de) | Verfahren zur herstellung neuer 1h, 3h-pyrrolo[1,2-c]thiazolderivate | |
| DE2505297A1 (de) | Neue 2-arylamino-2-imidazolinderivate und ein verfahren zu deren herstellung | |
| EP0019172B1 (de) | 6-Substituierte 11-Alkylen-morphantridine, Verfahren zu ihrer Herstellung und diese enthaltende therapeutische Mittel | |
| DE2424334A1 (de) | Verfahren zur herstellung neuer heterocyclischer verbindungen | |
| CH520680A (de) | Verfahren zur Herstellung neuer Mutterkornpeptidalkaloide | |
| DD210456A5 (de) | Verfahren zur herstellung von pyrazolopyridin-verbindungen | |
| DE3020267C2 (no) | ||
| EP0054839B1 (de) | 2-Acylaminomethyl-1,4-benzodiazepine und deren Salze sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2259471C2 (de) | 2-Halogen-9-phenyl-5,6-dihydro-7H-pyrido [2,3-f] [1,4] diazepinderivate | |
| EP0072029B1 (de) | Triazolobenzazepine, Verfahren und Zwischenprodukte zu deren Herstellung und diese enthaltende Arzneimittel | |
| EP0066774A1 (de) | Neue 1,4,9,10-Tetrahydro-pyrazolo(4,3-e)pyrido(3,2-b)(1,4)-diazepin-10-one, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| EP0045519B1 (de) | Pyrrolo(3,4-d)(2)benzazepine, Zwischenprodukte und Verfahren zu deren Herstellung sowie diese enthaltende Arzneimittel | |
| EP0045520B1 (de) | Pyrimido(4,5-d)(2)benzazepine, Verfahren für ihre Herstellung und diese enthaltende Arzneimittel | |
| EP0030015B1 (de) | Triazolobenzazepine, Zwischenprodukte und Verfahren zu ihrer Herstellung, sowie diese enthaltende Präparate | |
| EP0045521B1 (de) | Pyrazolobenzazepine, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
| EP0357043A2 (de) | Imidazodiazepin-Derivate | |
| EP0066303A1 (de) | 2-Azidomethyl-1,4-benzodiazepine und deren Salze sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| AT395154B (de) | Verfahren zur herstellung von neuen imidazo(1,5-a)(1,4)diazepinverbindungen | |
| CH634069A5 (en) | Process for preparing novel 7-substituted 7H-pyrrolo[3,2-f]quinazoline-1,3-diamines | |
| EP0041627B1 (de) | 3H-2-Benzazepine, Zwischenprodukte und Verfahren zu ihrer Herstellung, sowie diese enthaltende Präparate |