IL97307A - Hexahydrobenz [DC] indoles, a process for their preparation and pharmaceutical preparations that contain them - Google Patents

Hexahydrobenz [DC] indoles, a process for their preparation and pharmaceutical preparations that contain them

Info

Publication number: IL97307A
Authority: IL; Israel
Prior art keywords: amino; compound; hydrogen; indole; hexahydrobenz
Prior art date: 1990-02-26

Application number

IL9730791A

Other languages

English (en)

Hebrew (he)

Other versions

IL97307A0 (en

Original Assignee

Lilly Co Eli

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-02-26

Filing date

1991-02-20

Publication date

1995-06-29

1991-02-20 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1992-05-25 Publication of IL97307A0 publication Critical patent/IL97307A0/xx

1995-06-29 Publication of IL97307A publication Critical patent/IL97307A/en

Links

238000000034 method Methods 0.000 title claims description 31
230000008569 process Effects 0.000 title claims description 6
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
238000002360 preparation method Methods 0.000 title description 23
MFVFAPQCEUCUSG-UHFFFAOYSA-N 1,2,2a,3,4,5-hexahydrobenzo[cd]indole Chemical class C1CCC2CNC3=CC=CC1=C32 MFVFAPQCEUCUSG-UHFFFAOYSA-N 0.000 title description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 72
150000001875 compounds Chemical class 0.000 claims description 52
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 36
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 26
229910052739 hydrogen Inorganic materials 0.000 claims description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 17
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 13
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 10
-1 p_-toluenesulfonyl Chemical group 0.000 claims description 10
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
230000002083 iodinating effect Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 2
230000002152 alkylating effect Effects 0.000 claims description 2
239000000543 intermediate Substances 0.000 abstract description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 3
210000003169 central nervous system Anatomy 0.000 abstract description 2
JPTWSZJFCLJZJX-UHFFFAOYSA-N 1,3,4,5-tetrahydrobenzo[cd]indol-4-amine Chemical class C1=CC(CC(N)C2)=C3C2=CNC3=C1 JPTWSZJFCLJZJX-UHFFFAOYSA-N 0.000 abstract 1
GWGAULYPKADPCF-UHFFFAOYSA-N 6-iodo-1,2,2a,3,4,5-hexahydrobenzo[cd]indol-4-amine Chemical class C1NC2=CC=C(I)C3=C2C1CC(N)C3 GWGAULYPKADPCF-UHFFFAOYSA-N 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
239000007787 solid Substances 0.000 description 38
239000000203 mixture Substances 0.000 description 37
239000011541 reaction mixture Substances 0.000 description 37
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
239000000243 solution Substances 0.000 description 22
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
229910002091 carbon monoxide Inorganic materials 0.000 description 21
238000003756 stirring Methods 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
239000000047 product Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
229960000583 acetic acid Drugs 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 11
229910052740 iodine Inorganic materials 0.000 description 11
239000011630 iodine Substances 0.000 description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
238000004458 analytical method Methods 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
229910021529 ammonia Inorganic materials 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
238000004566 IR spectroscopy Methods 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
239000007858 starting material Substances 0.000 description 8
101150041968 CDC13 gene Proteins 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
239000012298 atmosphere Substances 0.000 description 7
229940086542 triethylamine Drugs 0.000 description 7
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
150000002431 hydrogen Chemical group 0.000 description 6
150000002475 indoles Chemical class 0.000 description 6
239000007788 liquid Substances 0.000 description 6
TWLXDPFBEPBAQB-UHFFFAOYSA-N orthoperiodic acid Chemical compound OI(O)(O)(O)(O)=O TWLXDPFBEPBAQB-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
150000001412 amines Chemical class 0.000 description 5
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 5
239000007789 gas Substances 0.000 description 5
229910052763 palladium Inorganic materials 0.000 description 5
239000012071 phase Substances 0.000 description 5
150000003335 secondary amines Chemical class 0.000 description 5
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 4
150000001414 amino alcohols Chemical class 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
230000026045 iodination Effects 0.000 description 4
238000006192 iodination reaction Methods 0.000 description 4
238000004811 liquid chromatography Methods 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 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
238000000870 ultraviolet spectroscopy Methods 0.000 description 4
102000035037 5-HT3 receptors Human genes 0.000 description 3
108091005477 5-HT3 receptors Proteins 0.000 description 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000003118 aryl group Chemical group 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 3
238000010926 purge Methods 0.000 description 3
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
125000004797 2,2,2-trichloroethoxy group Chemical group ClC(CO*)(Cl)Cl 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
238000007341 Heck reaction Methods 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
230000004075 alteration Effects 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000012267 brine Substances 0.000 description 2
238000005810 carbonylation reaction Methods 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
239000000376 reactant Substances 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
238000010956 selective crystallization Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000012265 solid product Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
238000012800 visualization Methods 0.000 description 2
RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
NDVDJYHPROIWDW-UHFFFAOYSA-N 2a,3,4,5-tetrahydro-2H-benzo[cd]indol-1-amine Chemical compound C1CCC2=CC=CC3=C2C1CN3N NDVDJYHPROIWDW-UHFFFAOYSA-N 0.000 description 1
125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
CLUUDXRMZOVVRW-UHFFFAOYSA-N 4-(dipropylamino)-1,2,2a,3,4,5-hexahydrobenzo[cd]indole-6-carboxamide Chemical compound C1NC2=CC=C(C(N)=O)C3=C2C1CC(N(CCC)CCC)C3 CLUUDXRMZOVVRW-UHFFFAOYSA-N 0.000 description 1
IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
CMQLMMHLMDOFBG-UHFFFAOYSA-N 6-bromo-1,2,2a,3,4,5-hexahydrobenzo[cd]indole Chemical class N1CC2CCCC3=C2C1=CC=C3Br CMQLMMHLMDOFBG-UHFFFAOYSA-N 0.000 description 1
MPBUVPPRHBECAK-UHFFFAOYSA-N 6-iodo-1,2,2a,3,4,5-hexahydrobenzo[cd]indole Chemical class N1CC2CCCC3=C2C1=CC=C3I MPBUVPPRHBECAK-UHFFFAOYSA-N 0.000 description 1
GRYNMIAIVVKWLW-UHFFFAOYSA-N 6-iodo-2a,3,4,5-tetrahydro-2H-benzo[cd]indol-1-amine Chemical compound NN1CC2C=3C(=C(C=CC13)I)CCC2 GRYNMIAIVVKWLW-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
241000694440 Colpidium aqueous Species 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
AAUHGKPIWCPHKM-UHFFFAOYSA-N [4-(dipropylamino)-2a,3,4,5-tetrahydro-2h-benzo[cd]indol-1-yl]-phenylmethanone Chemical compound C=12C3=CC=CC=1CC(N(CCC)CCC)CC2CN3C(=O)C1=CC=CC=C1 AAUHGKPIWCPHKM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
238000005915 ammonolysis reaction Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
150000001499 aryl bromides Chemical class 0.000 description 1
150000001503 aryl iodides Chemical class 0.000 description 1
150000001541 aziridines Chemical class 0.000 description 1
235000015241 bacon Nutrition 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000006229 carbon black Substances 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical group S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000008693 nausea Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
238000012856 packing Methods 0.000 description 1
150000002940 palladium Chemical class 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003140 primary amides Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003334 secondary amides Chemical class 0.000 description 1
239000000952 serotonin receptor agonist Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000010792 warming Methods 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
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/90—Benzo [c, d] indoles; Hydrogenated benzo [c, d] indoles
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

IL9730791A 1990-02-26 1991-02-20 Hexahydrobenz [DC] indoles, a process for their preparation and pharmaceutical preparations that contain them IL97307A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/485,193 US5039820A (en)	1990-02-26	1990-02-26	4-amino-6-iodo-hexahydrobenz(cd)indoles

Publications (2)

Publication Number	Publication Date
IL97307A0 IL97307A0 (en)	1992-05-25
IL97307A true IL97307A (en)	1995-06-29

Family

ID=23927258

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9730791A IL97307A (en)	1990-02-26	1991-02-20	Hexahydrobenz [DC] indoles, a process for their preparation and pharmaceutical preparations that contain them

Country Status (13)

Country	Link
US (1)	US5039820A (da)
EP (1)	EP0444853B1 (da)
JP (1)	JP3011465B2 (da)
KR (1)	KR0177166B1 (da)
AT (1)	ATE138911T1 (da)
CA (1)	CA2037116C (da)
DE (1)	DE69119933T2 (da)
DK (1)	DK0444853T3 (da)
ES (1)	ES2088460T3 (da)
GR (1)	GR3020474T3 (da)
HU (1)	HU219590B (da)
IE (1)	IE73230B1 (da)
IL (1)	IL97307A (da)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL97309A (en) *	1990-02-26	1996-11-14	Lilly Co Eli	Intermediates for hexahydrobenz Úcd¾ indoles and process for the preparation of pure enantiomers thereof
IL97308A (en) *	1990-02-26	1996-10-31	Lilly Co Eli	6-Substituted-hexahydrobenz (cd) indoles process for their preparation and pharmaceutical compositions containing them
US5302612A (en) *	1990-02-26	1994-04-12	Eli Lilly And Company	6-substituted-hexahydrobenz[cd]indoles
US5229409A (en) *	1990-08-15	1993-07-20	Eli Lilly And Company	6-substituted-tetrahydrobenz[cd]indoles
US5229410A (en) *	1990-08-15	1993-07-20	Eli Lilly And Company	6-substituted-hexahydrobenz[cd]indoles
US5364856A (en) *	1991-03-28	1994-11-15	Eli Lilly And Company	6-heterocyclic-4-amino-1,3,4,5-tetrahydrobenz[CD]indoles
US5347013A (en) *	1991-03-28	1994-09-13	Eli Lilly And Company	6-heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz[cd]indoles
US5643934A (en) *	1991-03-28	1997-07-01	Eli Lilly And Company	6-heterocyclic-4-amino-1,2,2a,3,4,5-hexahydrobenz [CD]indoles
US5385928A (en) *	1994-05-18	1995-01-31	Eli Lilly And Company	Tetrahydrobenz [CD] indazoles, compositions and use
US5498727A (en) *	1994-07-19	1996-03-12	Agouron Pharmaceuticals, Inc.	Preparation of benzindole compounds from naphthalene compounds
ZA9610853B (en) *	1995-12-29	1998-04-06	Smithkline Beecham Corp	Processes and intermediates for preparing pharmaceuticals.
TW430660B (en) *	1996-05-30	2001-04-21	Mochida Pharm Co Ltd	Novel benzindole derivatives for neuron cell protection, processes for production, and the pharmaceutical compounds containing them
KR20010035079A (ko) *	2000-12-16	2001-05-07	홍정원	바이오 보드 및 이 바이오 보드를 이용한 물품 보관함

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL74222A (en) *	1984-02-06	1988-07-31	Lilly Co Eli	6-substituted-4-dialkylamino tetrahydrobenz(c,d)indoles,their preparation and pharmaceutical compositions comprising them
DE3525564A1 (de) *	1985-07-15	1987-02-05	Schering Ag	Tricyclische verbindungen mit indolstruktur, verfahren zu ihrer herstellung und deren verwendung als arzneimittel
US5204340A (en) *	1989-04-11	1993-04-20	Eli Lilly And Company	Tetrahydrobenz(c,d)indole serotonin agonists

1990
- 1990-02-26 US US07/485,193 patent/US5039820A/en not_active Expired - Lifetime
1991
- 1991-02-20 IL IL9730791A patent/IL97307A/en not_active IP Right Cessation
- 1991-02-20 JP JP3048879A patent/JP3011465B2/ja not_active Expired - Fee Related
- 1991-02-25 IE IE62391A patent/IE73230B1/en not_active IP Right Cessation
- 1991-02-25 KR KR1019910003028A patent/KR0177166B1/ko not_active Expired - Fee Related
- 1991-02-25 HU HU27/91A patent/HU219590B/hu not_active IP Right Cessation
- 1991-02-26 EP EP91301502A patent/EP0444853B1/en not_active Expired - Lifetime
- 1991-02-26 ES ES91301502T patent/ES2088460T3/es not_active Expired - Lifetime
- 1991-02-26 DK DK91301502.0T patent/DK0444853T3/da active
- 1991-02-26 DE DE69119933T patent/DE69119933T2/de not_active Expired - Fee Related
- 1991-02-26 AT AT91301502T patent/ATE138911T1/de not_active IP Right Cessation
- 1991-02-26 CA CA002037116A patent/CA2037116C/en not_active Expired - Fee Related
1996
- 1996-07-09 GR GR960401842T patent/GR3020474T3/el unknown

Also Published As

Publication number	Publication date
KR910021374A (ko)	1991-12-20
IE73230B1 (en)	1997-05-21
HUT56540A (en)	1991-09-30
IE910623A1 (en)	1991-08-28
HU219590B (hu)	2001-05-28
KR0177166B1 (ko)	1999-03-20
DE69119933D1 (de)	1996-07-11
GR3020474T3 (en)	1996-10-31
US5039820A (en)	1991-08-13
EP0444853A2 (en)	1991-09-04
EP0444853B1 (en)	1996-06-05
IL97307A0 (en)	1992-05-25
DE69119933T2 (de)	1996-10-31
EP0444853A3 (en)	1992-02-19
CA2037116A1 (en)	1991-08-27
ES2088460T3 (es)	1996-08-16
DK0444853T3 (da)	1996-06-24
CA2037116C (en)	2003-10-28
ATE138911T1 (de)	1996-06-15
JPH04211652A (ja)	1992-08-03
JP3011465B2 (ja)	2000-02-21

Legal Events

Date	Code	Title
1997-06-10	KB	Patent renewed
2001-06-14	KB	Patent renewed
2006-01-15	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
US5536832A (en)	1996-07-16	N-acyl-2,3-benzodiazepine derivatives pharmaceutical compositions containing them and process for preparing same
US5039820A (en)	1991-08-13	4-amino-6-iodo-hexahydrobenz(cd)indoles
NO820937L (no)	1982-09-24	9-(2-(3-indolyl)etyl)-1-oksa-4,9-diazaspiro(5,5)-undekan-3-oner og fremgangsmaate for deres fremstilling
FI95464C (fi)	1996-02-12	Menetelmä terapeuttisesti käyttökelpoisen 4-(di-n-propyyli)amino-6-aminokarbonyyli-1,3,4,5-tetrahydrobentso/c,d/indolihippuraatin valmistam iseksi
EP0033767B1 (en)	1984-06-27	Indolobenzoxazines, processes for preparing and pharmaceutical compositions containing the same
CA2362700A1 (en)	2000-09-28	Tricyclic indole-2-carboxylic acid compound used as nmda receptor antagonist
US5318967A (en)	1994-06-07	2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole derivatives
KR100753353B1 (ko)	2007-08-30	졸미트립탄 화합물의 제조방법
AU752444B2 (en)	2002-09-19	Novel stereoselective processes for the preparation of gabapentin analogues
US5212319A (en)	1993-05-18	Intermediates to 4-amino-hexahydrobenz[cd]indoles and processes therefor
EP0444851B1 (en)	1995-09-06	Hexahydrobenz[CD]indoles and processes for preparation thereof
US5912365A (en)	1999-06-15	Derivatives of 2-azabicyclo 2.2.1! heptane, their preparation and their application
US4885364A (en)	1989-12-05	Resolution process for benzazepine intermediates
HU191535B (en)	1987-03-30	Process for producing 2-azabicyclo/2.2.2/octane derivatives
NO175680B (no)	1994-08-08	Fremgangsmåte for fremstilling av en 3-alkylert indol
SE437519B (sv)	1985-03-04	Pyrido/3,2,1-jk/karbazolderivat
Hwang et al.	1979	The Synthesis of 12‐Methyl‐1, 2, 3, 4, 6, 7, 12, 12B‐Octahydroindolo [2, 3‐A] Quinolizine (1), 1‐Benzoyl‐1, 2, 3, 4, 6, 7, 12, 12B‐Octahydroindolo [2, 3‐A] Quinolizine (2), and 1‐Phenylcarbinol‐1, 2, 3, 4, 6, 7, 12, 12B‐Octahydroindolo [2, 3‐A] Quinolizine (3)
HU198717B (en)	1989-11-28	New process for producing derivatives of catharantin and allocatharantin