NO751055L - - Google Patents
Info
- Publication number
- NO751055L NO751055L NO751055A NO751055A NO751055L NO 751055 L NO751055 L NO 751055L NO 751055 A NO751055 A NO 751055A NO 751055 A NO751055 A NO 751055A NO 751055 L NO751055 L NO 751055L
- Authority
- NO
- Norway
- Prior art keywords
- fluorophenyl
- tetrahydro
- fluoro
- carboline
- formula
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 54
- 229910052731 fluorine Inorganic materials 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 38
- 229910052739 hydrogen Chemical group 0.000 claims description 34
- 239000001257 hydrogen Chemical group 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 239000000460 chlorine Chemical group 0.000 claims description 24
- 239000011737 fluorine Substances 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- -1 bromobenzene compound Chemical class 0.000 claims description 17
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 12
- 150000008064 anhydrides Chemical class 0.000 claims description 11
- 150000002576 ketones Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 6
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 claims description 6
- 230000010933 acylation Effects 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000003333 secondary alcohols Chemical class 0.000 claims description 2
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 109
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 96
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 76
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 76
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- 229910001868 water Inorganic materials 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 239000000203 mixture Substances 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 238000004458 analytical method Methods 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000010992 reflux Methods 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 239000012458 free base Substances 0.000 description 10
- 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 239000012266 salt solution Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 229940025084 amphetamine Drugs 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 150000002475 indoles Chemical class 0.000 description 6
- 150000004031 phenylhydrazines Chemical class 0.000 description 6
- 230000001624 sedative effect Effects 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000000538 analytical sample Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000000932 sedative agent Substances 0.000 description 5
- PBUHAWCPUJZXSL-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2C2=C1CNC2 PBUHAWCPUJZXSL-UHFFFAOYSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 150000007857 hydrazones Chemical class 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- AIKRNPPDTQIQIZ-UHFFFAOYSA-N pyrrolo[3,4-b]indole Chemical group C1=CC=C2C3=CN=CC3=NC2=C1 AIKRNPPDTQIQIZ-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003204 tranquilizing agent Substances 0.000 description 4
- 230000002936 tranquilizing effect Effects 0.000 description 4
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- MDAGIYDZFPGBEP-UHFFFAOYSA-N 4-[7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-ol Chemical compound C=1C=C(F)C=CC=1C(O)CCCN(C1)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 MDAGIYDZFPGBEP-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- 238000003747 Grignard reaction Methods 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 238000006254 arylation reaction Methods 0.000 description 3
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- 229940067157 phenylhydrazine Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229940125723 sedative agent Drugs 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- YQVZREHUWCCHHX-UHFFFAOYSA-N (4-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Cl)C=C1 YQVZREHUWCCHHX-UHFFFAOYSA-N 0.000 description 2
- REUPXULKSZESBY-UHFFFAOYSA-N 1-[7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indol-1-yl]-3,3-dimethylbutan-1-one Chemical compound CC(C)(C)CC(=O)C1NCC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 REUPXULKSZESBY-UHFFFAOYSA-N 0.000 description 2
- UMTDBQHJIKJUGZ-UHFFFAOYSA-N 4-[7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-one;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C(=O)CCCN1CC(C=2C(=CC=C(F)C=2)N2C=3C=CC(F)=CC=3)=C2C1 UMTDBQHJIKJUGZ-UHFFFAOYSA-N 0.000 description 2
- TZWSURDURFBLQE-UHFFFAOYSA-N 4-[8-chloro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indol-2-yl]-1-(4-fluorophenyl)butan-1-ol;hydrochloride Chemical compound Cl.C=1C=C(F)C=CC=1C(O)CCCN(C1)CC2=C1C1=C(Cl)C=CC=C1N2C1=CC=C(F)C=C1 TZWSURDURFBLQE-UHFFFAOYSA-N 0.000 description 2
- RUWYUKDWFTUUJZ-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2,3-dihydro-1h-pyrrolo[3,4-b]indole;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1N1C2=CC=C(F)C=C2C2=C1CNC2 RUWYUKDWFTUUJZ-UHFFFAOYSA-N 0.000 description 2
- HZZHEIMZMCKOLL-UHFFFAOYSA-N 7-fluoro-4-(4-fluorophenyl)-2-(3-methylbutyl)-1,3-dihydropyrrolo[3,4-b]indole hydrochloride Chemical compound Cl.C1N(CCC(C)C)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 HZZHEIMZMCKOLL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 101001066681 Homo sapiens Integrase Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102100034353 Integrase Human genes 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- 241000124008 Mammalia Species 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
- LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 2
- JZKXHUGBKHTPCL-UHFFFAOYSA-N ethyl 7-fluoro-4-(4-fluorophenyl)-1,3-dihydropyrrolo[3,4-b]indole-2-carboxylate Chemical compound C1N(C(=O)OCC)CC2=C1C1=CC(F)=CC=C1N2C1=CC=C(F)C=C1 JZKXHUGBKHTPCL-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 150000005171 halobenzenes Chemical class 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase 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
- 238000001556 precipitation Methods 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45664074A | 1974-04-01 | 1974-04-01 | |
| US456641A US3925409A (en) | 1974-04-01 | 1974-04-01 | 4-Aryl-1,2,3,4-tetrahydropyrrolo{8 3,4-b{9 indoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO751055L true NO751055L (xx) | 1975-10-02 |
Family
ID=27038317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO751055A NO751055L (xx) | 1974-04-01 | 1975-03-25 |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS587635B2 (xx) |
| AR (2) | AR207799A1 (xx) |
| AU (1) | AU7955975A (xx) |
| DD (1) | DD118879A5 (xx) |
| DE (1) | DE2514084A1 (xx) |
| DK (2) | DK130575A (xx) |
| ES (3) | ES436157A1 (xx) |
| FI (1) | FI750940A (xx) |
| FR (1) | FR2265368A1 (xx) |
| IL (1) | IL46925A0 (xx) |
| LU (1) | LU72182A1 (xx) |
| NL (1) | NL7503700A (xx) |
| NO (1) | NO751055L (xx) |
| RO (1) | RO72884A (xx) |
| SE (2) | SE423630B (xx) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4224329A (en) * | 1979-01-23 | 1980-09-23 | Pfizer Inc. | 2-Substituted-trans-5-aryl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indoles |
| US4451655A (en) * | 1982-05-17 | 1984-05-29 | Pfizer Inc. | Process for preparing carboline derivatives and compounds used in their preparation |
| AU765751B2 (en) * | 1998-12-21 | 2003-09-25 | Janssen Pharmaceutica N.V. | Benzisoxazoles and phenones as alpha2-antagonists |
| RU2320662C1 (ru) * | 2006-08-24 | 2008-03-27 | Андрей Александрович Иващенко | ЗАМЕЩЕННЫЕ ПИРРОЛО[4,3-b]ИНДОЛЫ, КОМБИНАТОРНАЯ И ФОКУСИРОВАННАЯ БИБЛИОТЕКИ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЯ |
| US8993572B2 (en) * | 2010-04-22 | 2015-03-31 | Intra-Cellular Therapies, Inc. | Pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalines derivatives and [1,4]oxazino[2,3,4-hi]pyrido[4,3-b]indole derivatives |
-
1975
- 1975-01-01 AR AR261449A patent/AR207799A1/es active
- 1975-01-01 AR AR258188A patent/AR206812A1/es active
- 1975-03-14 SE SE7502927A patent/SE423630B/xx unknown
- 1975-03-25 IL IL46925A patent/IL46925A0/xx unknown
- 1975-03-25 NO NO751055A patent/NO751055L/no unknown
- 1975-03-26 AU AU79559/75A patent/AU7955975A/en not_active Expired
- 1975-03-26 DK DK130575A patent/DK130575A/da not_active Application Discontinuation
- 1975-03-27 NL NL7503700A patent/NL7503700A/xx not_active Application Discontinuation
- 1975-03-27 FI FI750940A patent/FI750940A/fi not_active Application Discontinuation
- 1975-03-29 DE DE19752514084 patent/DE2514084A1/de not_active Ceased
- 1975-03-31 ES ES436157A patent/ES436157A1/es not_active Expired
- 1975-04-01 RO RO7581868A patent/RO72884A/ro unknown
- 1975-04-01 LU LU72182A patent/LU72182A1/xx unknown
- 1975-04-01 JP JP50040224A patent/JPS587635B2/ja not_active Expired
- 1975-04-01 DD DD185114A patent/DD118879A5/xx unknown
- 1975-04-01 FR FR7510139A patent/FR2265368A1/fr active Granted
-
1976
- 1976-11-30 ES ES453788A patent/ES453788A1/es not_active Expired
- 1976-11-30 ES ES453787A patent/ES453787A1/es not_active Expired
-
1978
- 1978-05-01 DK DK187878A patent/DK187878A/da not_active Application Discontinuation
-
1982
- 1982-01-07 SE SE8200047A patent/SE8200047L/sv not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7502927L (xx) | 1975-10-02 |
| SE8200047L (sv) | 1982-01-07 |
| AR207799A1 (es) | 1976-10-29 |
| NL7503700A (nl) | 1975-10-03 |
| ES436157A1 (es) | 1977-04-16 |
| AR206812A1 (es) | 1976-08-23 |
| ES453787A1 (es) | 1978-01-01 |
| LU72182A1 (xx) | 1976-03-02 |
| JPS587635B2 (ja) | 1983-02-10 |
| RO72884A (ro) | 1983-08-03 |
| FR2265368A1 (en) | 1975-10-24 |
| RO72884B (ro) | 1983-07-30 |
| FI750940A (xx) | 1975-10-02 |
| IL46925A0 (en) | 1975-05-22 |
| SE423630B (sv) | 1982-05-17 |
| FR2265368B1 (xx) | 1978-07-28 |
| DD118879A5 (xx) | 1976-03-20 |
| ES453788A1 (es) | 1978-01-01 |
| DK130575A (xx) | 1975-10-02 |
| DE2514084A1 (de) | 1975-11-20 |
| JPS50140494A (xx) | 1975-11-11 |
| DK187878A (da) | 1978-05-01 |
| AU7955975A (en) | 1976-09-30 |
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