CA1055527A - Procedes pour la preparation de benzobicycloalkene amines et de composes connexes - Google Patents

Procedes pour la preparation de benzobicycloalkene amines et de composes connexes

Info

Publication number: CA1055527A
Authority: CA; Canada
Prior art keywords: compound; formula; ethyl; lower alkyl; methyl
Prior art date: 1973-10-15
Legal status (The legal status 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 status listed.): Expired

Application number

CA210,110A

Other languages

English (en)

Inventor

Meier E. Freed

John R. Potoski

Stanley C. Bell

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Wyeth LLC

Original Assignee

American Home Products Corp

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.)

1973-10-15

Filing date

1974-09-26

Publication date

1979-05-29

1974-09-26 Application filed by American Home Products Corp filed Critical American Home Products Corp

1979-05-29 Application granted granted Critical

1979-05-29 Publication of CA1055527A publication Critical patent/CA1055527A/fr

Status Expired legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title claims abstract description 32
150000001412 amines Chemical class 0.000 title claims abstract description 14
150000001875 compounds Chemical class 0.000 title claims description 163
238000000034 method Methods 0.000 title claims description 91
230000008569 process Effects 0.000 title claims description 74
125000000217 alkyl group Chemical group 0.000 claims abstract description 115
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 65
150000003839 salts Chemical class 0.000 claims description 61
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 58
239000002253 acid Substances 0.000 claims description 57
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 55
-1 alkali metal alkoxide Chemical class 0.000 claims description 48
239000001257 hydrogen Substances 0.000 claims description 45
229910052739 hydrogen Inorganic materials 0.000 claims description 45
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
150000002576 ketones Chemical class 0.000 claims description 33
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
239000000203 mixture Substances 0.000 claims description 27
125000003545 alkoxy group Chemical group 0.000 claims description 23
239000000126 substance Substances 0.000 claims description 23
239000002585 base Substances 0.000 claims description 22
229910052783 alkali metal Inorganic materials 0.000 claims description 21
230000009467 reduction Effects 0.000 claims description 21
238000006722 reduction reaction Methods 0.000 claims description 21
150000004678 hydrides Chemical class 0.000 claims description 20
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
150000001408 amides Chemical class 0.000 claims description 18
239000000460 chlorine Substances 0.000 claims description 18
150000002989 phenols Chemical class 0.000 claims description 17
125000001309 chloro group Chemical group Cl* 0.000 claims description 15
150000003141 primary amines Chemical class 0.000 claims description 14
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 12
230000003287 optical effect Effects 0.000 claims description 12
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
229910052794 bromium Chemical group 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
125000001033 ether group Chemical group 0.000 claims description 9
238000003776 cleavage reaction Methods 0.000 claims description 8
125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
230000007017 scission Effects 0.000 claims description 8
RMXLHIUHKIVPAB-OWOJBTEDSA-N (e)-1,4-dibromobut-2-ene Chemical compound BrC\C=C\CBr RMXLHIUHKIVPAB-OWOJBTEDSA-N 0.000 claims description 7
125000001246 bromo group Chemical group Br* 0.000 claims description 7
239000002841 Lewis acid Substances 0.000 claims description 6
150000007517 lewis acids Chemical class 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 4
238000006820 Bouveault-Blanc reduction reaction Methods 0.000 claims description 2
IHORUMCRPJHEEB-UHFFFAOYSA-N 1-ethyl-4-methoxytricyclo[7.4.1.02,7]tetradeca-2(7),3,5,11-tetraen-14-amine Chemical compound NC1C2(CC=CCC1CC1=C2C=C(C=C1)OC)CC IHORUMCRPJHEEB-UHFFFAOYSA-N 0.000 claims 2
DONFCAMIZWSTQQ-UHFFFAOYSA-N 14-amino-1-ethyltricyclo[7.4.1.02,7]tetradeca-2(7),3,5,11-tetraen-4-ol Chemical compound NC1C2(CC=CCC1CC1=C2C=C(C=C1)O)CC DONFCAMIZWSTQQ-UHFFFAOYSA-N 0.000 claims 2
239000003153 chemical reaction reagent Substances 0.000 claims 1
229940126540 compound 41 Drugs 0.000 claims 1
239000000730 antalgic agent Substances 0.000 abstract description 8
239000000543 intermediate Substances 0.000 abstract description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
238000007792 addition Methods 0.000 description 40
239000000243 solution Substances 0.000 description 35
239000000047 product Substances 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 22
125000003342 alkenyl group Chemical group 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
150000002431 hydrogen Chemical group 0.000 description 18
150000003335 secondary amines Chemical group 0.000 description 15
239000002904 solvent Substances 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
125000000304 alkynyl group Chemical group 0.000 description 12
150000002923 oximes Chemical class 0.000 description 12
238000003756 stirring Methods 0.000 description 11
150000003512 tertiary amines Chemical class 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
238000001953 recrystallisation Methods 0.000 description 10
238000001914 filtration Methods 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
238000010992 reflux Methods 0.000 description 8
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
150000001350 alkyl halides Chemical class 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000010561 standard procedure Methods 0.000 description 6
239000007858 starting material Substances 0.000 description 6
238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
239000003921 oil Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
IJYWCVPWBNPSIL-UHFFFAOYSA-N 1-ethyl-7-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=C(OC)C=C2C(CC)C(=O)CCC2=C1 IJYWCVPWBNPSIL-UHFFFAOYSA-N 0.000 description 4
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 4
SFRFIDSLKKHXIY-UHFFFAOYSA-N 4-methoxy-1-methyltricyclo[7.4.1.02,7]tetradeca-2(7),3,5,11-tetraen-14-one Chemical compound COC1=CC2=C(CC3CC=CCC2(C3=O)C)C=C1 SFRFIDSLKKHXIY-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
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 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
230000000202 analgesic effect Effects 0.000 description 4
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
239000012458 free base Substances 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000005932 reductive alkylation reaction Methods 0.000 description 4
238000000926 separation method Methods 0.000 description 4
FQDIANVAWVHZIR-UPHRSURJSA-N (z)-1,4-dichlorobut-2-ene Chemical compound ClC\C=C/CCl FQDIANVAWVHZIR-UPHRSURJSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
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 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
241000700159 Rattus Species 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
238000002955 isolation Methods 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000000638 solvent extraction Methods 0.000 description 3
ZNYHFLDXLXGVQP-UHFFFAOYSA-N tricyclo[7.4.1.02,7]tetradeca-2,4,6-trien-14-amine Chemical class C1=CC=CC2=C1CC1CCCCC2C1N ZNYHFLDXLXGVQP-UHFFFAOYSA-N 0.000 description 3
PUSJPZXVRHKDAL-UHFFFAOYSA-N 1-ethyl-4-methoxytricyclo[7.4.1.02,7]tetradeca-2(7),3,5,11-tetraen-14-one Chemical compound C(C)C12CC=CCC(CC3=C1C=C(C=C3)OC)C2=O PUSJPZXVRHKDAL-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
IAQRGUVFOMOMEM-UHFFFAOYSA-N but-2-ene Chemical compound CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 2
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000006266 etherification reaction Methods 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000008188 pellet Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
230000003595 spectral effect Effects 0.000 description 2
238000012360 testing method Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
QJROBOZHIDRCBD-UHFFFAOYSA-N tricyclo[7.4.1.02,7]tetradeca-2,4,6,11-tetraen-14-amine Chemical class C1=CC=CC2=C1CC1CC=CCC2C1N QJROBOZHIDRCBD-UHFFFAOYSA-N 0.000 description 2
KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical class C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000006024 2-pentenyl group Chemical group 0.000 description 1
125000000094 2-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
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical class C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 1
FCIOSABEPQCFHA-UHFFFAOYSA-N 4-methoxy-1-methyltricyclo[7.4.1.02,7]tetradeca-2(7),3,5-trien-14-amine Chemical compound C1CCCC2(C)C3=CC(OC)=CC=C3CC1C2N FCIOSABEPQCFHA-UHFFFAOYSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
241000272194 Ciconiiformes Species 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
238000003833 Wallach reaction Methods 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
238000010171 animal model Methods 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000000969 carrier Substances 0.000 description 1
229940000425 combination drug Drugs 0.000 description 1
239000013078 crystal Substances 0.000 description 1
229960001270 d- tartaric acid Drugs 0.000 description 1
238000005661 deetherification reaction Methods 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 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
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical class OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
229940032007 methylethyl ketone Drugs 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
ONPRFAGFWVXEOK-UHFFFAOYSA-N n,n-diethyl-1-(4-methylphenyl)hex-5-en-1-yn-3-amine Chemical compound CCN(CC)C(CC=C)C#CC1=CC=C(C)C=C1 ONPRFAGFWVXEOK-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000005646 oximino group Chemical group 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000004044 response Effects 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
238000010998 test method 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
238000000844 transformation Methods 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
239000012905 visible particle Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
- C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
- C07C49/755—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups a keto group being part of a condensed ring system with two or three rings, at least one ring being a six-membered aromatic ring
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA210,110A 1973-10-15 1974-09-26 Procedes pour la preparation de benzobicycloalkene amines et de composes connexes Expired CA1055527A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US40652173A	1973-10-15	1973-10-15
GB1141074		1974-03-14

Publications (1)

Publication Number	Publication Date
CA1055527A true CA1055527A (fr)	1979-05-29

Family

ID=26248260

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA210,110A Expired CA1055527A (fr)	1973-10-15	1974-09-26	Procedes pour la preparation de benzobicycloalkene amines et de composes connexes

Country Status (5)

Country	Link
JP (2)	JPS5537988B2 (fr)
CA (1)	CA1055527A (fr)
CH (1)	CH617664A5 (fr)
FR (1)	FR2279384A1 (fr)
NL (1)	NL7413487A (fr)

1974
- 1974-09-26 CA CA210,110A patent/CA1055527A/fr not_active Expired
- 1974-10-14 NL NL7413487A patent/NL7413487A/xx not_active Application Discontinuation
- 1974-10-14 FR FR7434504A patent/FR2279384A1/fr active Granted
- 1974-10-15 JP JP11914574A patent/JPS5537988B2/ja not_active Expired
- 1974-10-15 CH CH1383974A patent/CH617664A5/fr not_active IP Right Cessation
1978
- 1978-05-29 JP JP53064851A patent/JPS5811420B2/ja not_active Expired

Also Published As

Publication number	Publication date
FR2279384A1 (fr)	1976-02-20
JPS5064256A (fr)	1975-05-31
FR2279384B1 (fr)	1978-07-21
JPS5439062A (en)	1979-03-24
NL7413487A (nl)	1975-04-17
JPS5537988B2 (fr)	1980-10-01
CH617664A5 (en)	1980-06-13
JPS5811420B2 (ja)	1983-03-02

Publication	Publication Date	Title
US4316043A (en)	1982-02-16	[(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids and their analogs, esters, salts and derivatives
JP2637737B2 (ja)	1997-08-06	新規な薬剤
US4317922A (en)	1982-03-02	[(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids and their analogs, esters, salts and derivatives
US4337354A (en)	1982-06-29	[(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoic and cycloalkanoic acids, their analogs, esters, salts, and derivatives
Belleau	1957	Synthesis in the Field of the Erythrina Alkaloids: Part I. The Synthesis of Hexahydroapoerysotrine
MAY et al.	1955	Structures related to morphine. III. Synthesis of an analog of N-methylmorphinan
US4076953A (en)	1978-02-28	1,3-Bridged amino tetralins
US4272533A (en)	1981-06-09	N-Phenylindoline derivatives, and pharmaceutical compositions containing them
CA1055527A (fr)	1979-05-29	Procedes pour la preparation de benzobicycloalkene amines et de composes connexes
US3372193A (en)	1968-03-05	1, 1-diaryl-2-methyl-3-(benzylidene-amino) propan-(1)-ols
US3317527A (en)	1967-05-02	3a and 5a tertiaryamino cycloalkylene of 5 to 7[alpha]benzofuranols
JPS6011901B2 (ja)	1985-03-28	新規の脂肪族置換された４−フエニル−ピペリジン
US3989717A (en)	1976-11-02	Indolobenzazepine derivatives
US5128369A (en)	1992-07-07	Arylalkylamine derivatives
KR880001298B1 (ko)	1988-07-22	벤조일-페닐-피페리딘 유도체의 제법
Cooper	1970	Stereospecific synthesis of cis-and trans-2-(3, 4, 5-trimethoxyphenyl)-cyclopropylamines
AU603081B2 (en)	1990-11-08	Symmetrical O-substituted dioximes of benzo-fused beta- diketocycloalkylenes, the processes for their preparation and their application as drugs
CA1172263A (fr)	1984-08-07	3-aryl-2-cycloalcen-1-one substituee et methode de preparation
Cardwell et al.	1949	151. Experiments on the synthesis of substances related to the sterols. Part XLVI. The synthetic use of 4-keto-1: 1-dialkylpiperidinium salts
US3860652A (en)	1975-01-14	8-Aminoalkyl substituted dibenzobicyclo {8 3.2.1{9 {0 octadienes
EP0000825B1 (fr)	1982-04-14	Dérivés de l'indène à deux substituants géminaux, leurs procédés de préparation et compositions pharmaceutiques les contenant
CS235057B2 (en)	1985-04-16	Method of arylphenylnaphtalen derivatives production
US3558599A (en)	1971-01-26	1-(2-(alpha-alkoxybenzyl and substituted benzyl)cycloalkyl)heterocyclic amines
US3281468A (en)	1966-10-25	beta-phenyl-beta-hydroxyethylamines
US3527806A (en)	1970-09-08	10-alkyl-alkenyl- or benzyl-5-(3-aminopropylidene)-dibenzo(a,d)cycloheptenes