JP2003519209A - アミノメチル−フェニル−シクロヘキサノン誘導体 - Google Patents
アミノメチル−フェニル−シクロヘキサノン誘導体Info
- Publication number
- JP2003519209A JP2003519209A JP2001550191A JP2001550191A JP2003519209A JP 2003519209 A JP2003519209 A JP 2003519209A JP 2001550191 A JP2001550191 A JP 2001550191A JP 2001550191 A JP2001550191 A JP 2001550191A JP 2003519209 A JP2003519209 A JP 2003519209A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- mono
- alkyl
- phenyl
- Prior art date
- 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.)
- Pending
Links
- NWSCVDPHHGDSBE-UHFFFAOYSA-N 2-(aminomethyl)-2-phenylcyclohexan-1-one Chemical class C=1C=CC=CC=1C1(CN)CCCCC1=O NWSCVDPHHGDSBE-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 94
- 125000004432 carbon atom Chemical group C* 0.000 claims description 89
- 229910052799 carbon Inorganic materials 0.000 claims description 67
- -1 substituted - Chemical class 0.000 claims description 67
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical class [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 64
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 54
- 229910052801 chlorine Inorganic materials 0.000 claims description 53
- 229910052731 fluorine Inorganic materials 0.000 claims description 52
- 229910052717 sulfur Inorganic materials 0.000 claims description 52
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- 150000001875 compounds Chemical class 0.000 claims description 43
- 229910052740 iodine Inorganic materials 0.000 claims description 36
- 229910052794 bromium Inorganic materials 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 32
- 239000000126 substance Substances 0.000 claims description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- 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 claims description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 239000000047 product Substances 0.000 claims description 19
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 206010049119 Emotional distress Diseases 0.000 claims description 9
- 230000009429 distress Effects 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- UFXPDNGKMSEVHV-DOMZBBRYSA-N (3r,4s)-4-[(dimethylamino)methyl]-3-(3-hydroxyphenyl)cyclohexan-1-one Chemical compound CN(C)C[C@H]1CCC(=O)C[C@H]1C1=CC=CC(O)=C1 UFXPDNGKMSEVHV-DOMZBBRYSA-N 0.000 claims description 8
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- LXHDCSRTANCMGD-UHFFFAOYSA-N CN(C)CC1CC=CC(=O)C1C2=CC(=CC=C2)OC Chemical compound CN(C)CC1CC=CC(=O)C1C2=CC(=CC=C2)OC LXHDCSRTANCMGD-UHFFFAOYSA-N 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 6
- PKXKHMUMACVYHM-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-hydroxy-3-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC(C2(O)C(CCC(=O)C2)CN(C)C)=C1 PKXKHMUMACVYHM-UHFFFAOYSA-N 0.000 claims description 5
- GBJBAKOEQBLBPL-HIFRSBDPSA-N CN(C)C[C@H]1CCC(=O)C[C@H]1C1=CC=CC=C1 Chemical compound CN(C)C[C@H]1CCC(=O)C[C@H]1C1=CC=CC=C1 GBJBAKOEQBLBPL-HIFRSBDPSA-N 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- NHFVEBWIBVLQKP-UHFFFAOYSA-N 3,3-dimethyl-1,5-dioxaspiro[5.5]undecan-10-one Chemical compound O1CC(C)(C)COC11CC(=O)CCC1 NHFVEBWIBVLQKP-UHFFFAOYSA-N 0.000 claims 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 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- HJPSHWFGNDBKHV-BBRMVZONSA-N (3R,4R)-4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC([C@H]2[C@@H](CCC(=O)C2)CN(C)C)=C1 HJPSHWFGNDBKHV-BBRMVZONSA-N 0.000 claims description 3
- HJPSHWFGNDBKHV-CJNGLKHVSA-N (3R,4S)-4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohexan-1-one Chemical compound COC1=CC=CC([C@H]2[C@H](CCC(=O)C2)CN(C)C)=C1 HJPSHWFGNDBKHV-CJNGLKHVSA-N 0.000 claims description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
- GBJBAKOEQBLBPL-ZFWWWQNUSA-N CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC=C1 Chemical compound CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC=C1 GBJBAKOEQBLBPL-ZFWWWQNUSA-N 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 230000007794 irritation Effects 0.000 claims description 3
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 claims 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 claims description 2
- UFXPDNGKMSEVHV-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-hydroxyphenyl)cyclohexan-1-one Chemical compound CN(C)CC1CCC(=O)CC1C1=CC=CC(O)=C1 UFXPDNGKMSEVHV-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010011224 Cough Diseases 0.000 claims description 2
- 208000007882 Gastritis Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 208000018569 Respiratory Tract disease Diseases 0.000 claims description 2
- 206010001584 alcohol abuse Diseases 0.000 claims description 2
- 208000025746 alcohol use disease Diseases 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 238000006266 etherification reaction Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- CASUWPDYGGAUQV-UHFFFAOYSA-M potassium;methanol;hydroxide Chemical compound [OH-].[K+].OC CASUWPDYGGAUQV-UHFFFAOYSA-M 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 30
- NKJLGNHULJVJGL-UHFFFAOYSA-N 2-methyl-2-phenylcyclohexan-1-one Chemical class C=1C=CC=CC=1C1(C)CCCCC1=O NKJLGNHULJVJGL-UHFFFAOYSA-N 0.000 claims 2
- SROFOCUMLZWZIM-WFASDCNBSA-N CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC(F)=C1 Chemical compound CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC(F)=C1 SROFOCUMLZWZIM-WFASDCNBSA-N 0.000 claims 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- SROFOCUMLZWZIM-DOMZBBRYSA-N CN(C)C[C@H]1CCC(=O)C[C@H]1C1=CC=CC(F)=C1 Chemical compound CN(C)C[C@H]1CCC(=O)C[C@H]1C1=CC=CC(F)=C1 SROFOCUMLZWZIM-DOMZBBRYSA-N 0.000 claims 1
- YCAPYWSXKHDVND-KBPBESRZSA-N CN(C)C[C@H]1[C@@H](CCCC1=O)C2=CC(=CC=C2)O Chemical compound CN(C)C[C@H]1[C@@H](CCCC1=O)C2=CC(=CC=C2)O YCAPYWSXKHDVND-KBPBESRZSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 230000006698 induction Effects 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000005051 trimethylchlorosilane Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 5
- PZIXJJVOIDYJIW-UHFFFAOYSA-N CN(C)CC1CC=CC(=O)C1C2=CC(=CC=C2)OC.Cl Chemical compound CN(C)CC1CC=CC(=O)C1C2=CC(=CC=C2)OC.Cl PZIXJJVOIDYJIW-UHFFFAOYSA-N 0.000 description 5
- UFXPDNGKMSEVHV-WFASDCNBSA-N CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC(O)=C1 Chemical compound CN(C)C[C@@H]1CCC(=O)C[C@H]1C1=CC=CC(O)=C1 UFXPDNGKMSEVHV-WFASDCNBSA-N 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 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
- 239000006196 drop Substances 0.000 description 3
- YCOZIPAWZNQLMR-UHFFFAOYSA-N heptane - octane Natural products CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 3
- FGYDZOTXFUROMF-LINSIKMZSA-N (3R,4R)-4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohexan-1-one hydrochloride Chemical compound Cl.CN(C)C[C@H]1[C@@H](CC(CC1)=O)C1=CC(=CC=C1)OC FGYDZOTXFUROMF-LINSIKMZSA-N 0.000 description 2
- FGYDZOTXFUROMF-CACIRBSMSA-N (3R,4S)-4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohexan-1-one hydrochloride Chemical compound Cl.CN(C)C[C@@H]1[C@@H](CC(CC1)=O)C1=CC(=CC=C1)OC FGYDZOTXFUROMF-CACIRBSMSA-N 0.000 description 2
- VYUKCVLHGXBZDF-UHFFFAOYSA-N 3-methoxycyclohexan-1-one Chemical compound COC1CCCC(=O)C1 VYUKCVLHGXBZDF-UHFFFAOYSA-N 0.000 description 2
- GBJPHWSARPWFGF-UHFFFAOYSA-N 9-[(dimethylamino)methyl]-1,5-dioxaspiro[5.5]undecan-10-one Chemical compound C1C(=O)C(CN(C)C)CCC21OCCCO2 GBJPHWSARPWFGF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| DE10000311.7 | 2000-01-05 | ||
| DE10000311A DE10000311A1 (de) | 2000-01-05 | 2000-01-05 | Aminomethyl-Phonyl-Cyclohexanonderivate |
| PCT/EP2000/013282 WO2001049651A2 (de) | 2000-01-05 | 2000-12-27 | Aminomethyl-phenyl-cyclohexanonderivate |
Publications (2)
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| JP2003519209A true JP2003519209A (ja) | 2003-06-17 |
| JP2003519209A5 JP2003519209A5 (enExample) | 2008-02-21 |
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| CZ (1) | CZ20022338A3 (enExample) |
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| IL (2) | IL150558A0 (enExample) |
| MX (1) | MXPA02006697A (enExample) |
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| PE (1) | PE20011043A1 (enExample) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006527178A (ja) * | 2003-06-06 | 2006-11-30 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換された３−アリールブチル−アミン−化合物の製造方法 |
| JP2009096744A (ja) * | 2007-10-15 | 2009-05-07 | Nippon Soda Co Ltd | 環状アミノエーテルを用いたマンニッヒ反応 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7457762B2 (en) * | 2001-09-04 | 2008-11-25 | Accenture Global Services Gmbh | Optimization of management of maintenance, repair and overhaul of equipment in a specified time window |
| DE10328316A1 (de) | 2003-06-23 | 2005-01-20 | Grünenthal GmbH | Verfahren zur Herstellung von Dimethyl-(3-aryl-buthyl)-aminverbindungen als pharmazeutische Wirkstoffe |
| US7260408B2 (en) * | 2004-02-20 | 2007-08-21 | Airespace, Inc. | Wireless node location mechanism using antenna pattern diversity to enhance accuracy of location estimates |
| US20050236892A1 (en) * | 2004-04-27 | 2005-10-27 | Akihito Kusano | Hydraulic braking pressure generating apparatus for vehicles |
| DE102005052588A1 (de) | 2005-11-02 | 2007-05-10 | Grünenthal GmbH | Verfahren zur Herstellung substituierter Dimethyl-(3-aryl-butyl)-amin-Verbindungen mittels homogener Katalyse |
| TWI448447B (zh) | 2006-07-24 | 2014-08-11 | Gruenenthal Chemie | 製備（１ｒ，２ｒ）-３-（３-二甲胺基-１-乙基-２-甲基-丙基）-酚之方法 |
| EP2262759A1 (de) * | 2008-02-29 | 2010-12-22 | Grünenthal GmbH | Verfahren zur herstellung von (1rs,3rs,6rs)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexan-1,3-diol |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50157342A (enExample) * | 1974-03-04 | 1975-12-19 | ||
| JPS51143650A (en) * | 1975-06-06 | 1976-12-10 | Takeda Chem Ind Ltd | A process for preparing cyclohexanol derivatives |
| JPH0931033A (ja) * | 1995-07-11 | 1997-02-04 | Gruenenthal Gmbh | 医薬有効物質としての６− ジメチルアミノメチル− １− フエニル− シクロヘキサン化合物 |
| JPH09221460A (ja) * | 1995-12-20 | 1997-08-26 | Gruenenthal Gmbh | 医薬有効物質としての１− フエニル− ２− ジメチルアミノメチル− シクロヘキサン− １− オール− 化合物 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1518663A1 (de) * | 1965-08-02 | 1969-12-18 | Gruenenthal Chemie | Basisch substituierte Cycloalken-derivate und Verfahren zu ihrer Herstellung |
| US3652589A (en) * | 1967-07-27 | 1972-03-28 | Gruenenthal Chemie | 1-(m-substituted phenyl)-2-aminomethyl cyclohexanols |
| ATE147732T1 (de) | 1989-03-08 | 1997-02-15 | Merck Sharp & Dohme | Tetrahydroquinolin-derivate, verwendbar bei neurodegenerativen krankheiten |
| IL112569A (en) * | 1994-02-10 | 1999-12-22 | Wyeth John & Brother Ltd | Pharmaceutical compositions comprising cyclohexylamine derivatives certain such novel compounds and their preparation |
| DE19609847A1 (de) * | 1996-03-13 | 1997-09-18 | Gruenenthal Gmbh | Dimethyl-(3-aryl-but-3-enyl)-aminverbindungen als pharmazeutische Wirkstoffe |
| MY125037A (en) | 1998-06-10 | 2006-07-31 | Glaxo Wellcome Spa | 1,2,3,4 tetrahydroquinoline derivatives |
| DE19830105C1 (de) * | 1998-07-06 | 2000-02-17 | Gruenenthal Gmbh | Acridinderivate |
-
2000
- 2000-01-05 DE DE10000311A patent/DE10000311A1/de not_active Withdrawn
- 2000-12-27 CN CNB008192669A patent/CN100467441C/zh not_active Expired - Fee Related
- 2000-12-27 PL PL00356642A patent/PL356642A1/xx unknown
- 2000-12-27 IL IL15055800A patent/IL150558A0/xx active IP Right Grant
- 2000-12-27 JP JP2001550191A patent/JP2003519209A/ja active Pending
- 2000-12-27 KR KR1020027008706A patent/KR100748378B1/ko not_active Expired - Fee Related
- 2000-12-27 RU RU2002120897/04A patent/RU2002120897A/ru unknown
- 2000-12-27 CA CA002396310A patent/CA2396310A1/en not_active Abandoned
- 2000-12-27 HU HU0203859A patent/HUP0203859A3/hu unknown
- 2000-12-27 SI SI200030587T patent/SI1246791T1/xx unknown
- 2000-12-27 WO PCT/EP2000/013282 patent/WO2001049651A2/de not_active Ceased
- 2000-12-27 MX MXPA02006697A patent/MXPA02006697A/es active IP Right Grant
- 2000-12-27 DK DK00990824T patent/DK1246791T3/da active
- 2000-12-27 AT AT00990824T patent/ATE280752T1/de active
- 2000-12-27 SK SK980-2002A patent/SK286799B6/sk not_active IP Right Cessation
- 2000-12-27 PT PT00990824T patent/PT1246791E/pt unknown
- 2000-12-27 AU AU30169/01A patent/AU782862B2/en not_active Ceased
- 2000-12-27 BR BR0016941-2A patent/BR0016941A/pt not_active Application Discontinuation
- 2000-12-27 NZ NZ520468A patent/NZ520468A/en unknown
- 2000-12-27 ES ES00990824T patent/ES2231304T3/es not_active Expired - Lifetime
- 2000-12-27 CZ CZ20022338A patent/CZ20022338A3/cs unknown
- 2000-12-27 DE DE50008447T patent/DE50008447D1/de not_active Expired - Lifetime
- 2000-12-27 EP EP20000990824 patent/EP1246791B1/de not_active Expired - Lifetime
-
2001
- 2001-01-02 AR ARP010100008A patent/AR030683A1/es unknown
- 2001-01-04 CO CO01000529A patent/CO5261627A1/es not_active Application Discontinuation
- 2001-01-04 PE PE2001000012A patent/PE20011043A1/es not_active Application Discontinuation
-
2002
- 2002-06-20 NO NO20022983A patent/NO20022983L/no not_active Application Discontinuation
- 2002-07-03 IL IL150558A patent/IL150558A/en not_active IP Right Cessation
- 2002-07-05 US US10/189,184 patent/US6890959B2/en not_active Expired - Fee Related
- 2002-08-01 ZA ZA200206150A patent/ZA200206150B/xx unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50157342A (enExample) * | 1974-03-04 | 1975-12-19 | ||
| JPS51143650A (en) * | 1975-06-06 | 1976-12-10 | Takeda Chem Ind Ltd | A process for preparing cyclohexanol derivatives |
| JPH0931033A (ja) * | 1995-07-11 | 1997-02-04 | Gruenenthal Gmbh | 医薬有効物質としての６− ジメチルアミノメチル− １− フエニル− シクロヘキサン化合物 |
| JPH09221460A (ja) * | 1995-12-20 | 1997-08-26 | Gruenenthal Gmbh | 医薬有効物質としての１− フエニル− ２− ジメチルアミノメチル− シクロヘキサン− １− オール− 化合物 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006527178A (ja) * | 2003-06-06 | 2006-11-30 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換された３−アリールブチル−アミン−化合物の製造方法 |
| JP4848268B2 (ja) * | 2003-06-06 | 2011-12-28 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換された３−アリールブチル−アミン−化合物の製造方法 |
| JP2009096744A (ja) * | 2007-10-15 | 2009-05-07 | Nippon Soda Co Ltd | 環状アミノエーテルを用いたマンニッヒ反応 |
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