CZ20022338A3 - Deriváty aminomethyl-fenyl-cyklohexanu, způsob jejich výroby, léčiva tyto látky obsahující a jejich pouľití - Google Patents
Deriváty aminomethyl-fenyl-cyklohexanu, způsob jejich výroby, léčiva tyto látky obsahující a jejich pouľití Download PDFInfo
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- CZ20022338A3 CZ20022338A3 CZ20022338A CZ20022338A CZ20022338A3 CZ 20022338 A3 CZ20022338 A3 CZ 20022338A3 CZ 20022338 A CZ20022338 A CZ 20022338A CZ 20022338 A CZ20022338 A CZ 20022338A CZ 20022338 A3 CZ20022338 A3 CZ 20022338A3
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- Czechia
- Prior art keywords
- group
- unsubstituted
- carbon atoms
- mono
- polysubstituted
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- 239000003814 drug Substances 0.000 title claims abstract description 23
- 238000000034 method Methods 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims description 49
- 238000002360 preparation method Methods 0.000 title claims description 11
- ULRBJKIRTCBMRW-UHFFFAOYSA-N (1-phenylcyclohexyl)methanamine Chemical class C=1C=CC=CC=1C1(CN)CCCCC1 ULRBJKIRTCBMRW-UHFFFAOYSA-N 0.000 title claims 2
- NWSCVDPHHGDSBE-UHFFFAOYSA-N 2-(aminomethyl)-2-phenylcyclohexan-1-one Chemical class C=1C=CC=CC=1C1(CN)CCCCC1=O NWSCVDPHHGDSBE-UHFFFAOYSA-N 0.000 claims abstract description 38
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 427
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 161
- 229910052799 carbon Inorganic materials 0.000 claims description 128
- 229910052739 hydrogen Inorganic materials 0.000 claims description 127
- 239000001257 hydrogen Substances 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 121
- 229920006395 saturated elastomer Polymers 0.000 claims description 96
- 125000003342 alkenyl group Chemical group 0.000 claims description 89
- 125000000304 alkynyl group Chemical group 0.000 claims description 82
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- 229910052760 oxygen Inorganic materials 0.000 claims description 59
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 58
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 58
- 239000001301 oxygen Substances 0.000 claims description 58
- 229910052717 sulfur Inorganic materials 0.000 claims description 58
- 239000011593 sulfur Substances 0.000 claims description 58
- 229910052801 chlorine Inorganic materials 0.000 claims description 54
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 239000000460 chlorine Chemical group 0.000 claims description 52
- 229910052731 fluorine Inorganic materials 0.000 claims description 52
- 239000011737 fluorine Chemical group 0.000 claims description 52
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 39
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 38
- -1 rac-phenyl [4-Dimethylaminomethyl-3- (3-methoxy-phenyl) -cyclohexanone] Chemical compound 0.000 claims description 37
- 229910052794 bromium Inorganic materials 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 31
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 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 18
- 239000002253 acid Substances 0.000 claims description 18
- 239000002585 base Substances 0.000 claims description 18
- 150000007513 acids Chemical class 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- 208000002193 Pain Diseases 0.000 claims description 12
- 150000003840 hydrochlorides Chemical class 0.000 claims description 11
- 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 10
- 230000036407 pain Effects 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
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 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 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 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
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 7
- QRQZXONDVGVNQH-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohex-2-en-1-one Chemical compound COC1=CC=CC(C=2C(CCC(=O)C=2)CN(C)C)=C1 QRQZXONDVGVNQH-UHFFFAOYSA-N 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 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 5
- BAPSMKYJGSSKKI-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-4-[(dimethylamino)methyl]cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC(F)=CC(F)=C1 BAPSMKYJGSSKKI-UHFFFAOYSA-N 0.000 claims description 5
- UJAURWYSPLJUMU-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(4-methoxyphenyl)cyclohex-2-en-1-one Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)CCC1CN(C)C UJAURWYSPLJUMU-UHFFFAOYSA-N 0.000 claims description 5
- KMCQGZMJLRZRSV-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(6-methoxynaphthalen-2-yl)cyclohex-2-en-1-one Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C1=CC(=O)CCC1CN(C)C KMCQGZMJLRZRSV-UHFFFAOYSA-N 0.000 claims description 5
- QSYOGYPHPHSUMF-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-naphthalen-2-ylcyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=C(C=CC=C2)C2=C1 QSYOGYPHPHSUMF-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 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 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000012467 final product Substances 0.000 claims description 5
- 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 4
- IANBCHYJKGEOEV-UHFFFAOYSA-N 3-(3,5-dichlorophenyl)-4-[(dimethylamino)methyl]cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC(Cl)=CC(Cl)=C1 IANBCHYJKGEOEV-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
- NCZWDXKBNIMFQP-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-fluorophenyl)cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=CC(F)=C1 NCZWDXKBNIMFQP-UHFFFAOYSA-N 0.000 claims description 4
- FQUDADXUSNUPMC-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-hydroxyphenyl)cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=CC(O)=C1 FQUDADXUSNUPMC-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 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
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- KQKZQCQYVBWYHB-UHFFFAOYSA-N 3-[3-(difluoromethyl)phenyl]-4-[(dimethylamino)methyl]cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=CC(C(F)F)=C1 KQKZQCQYVBWYHB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 3
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 208000003251 Pruritus Diseases 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 230000007803 itching Effects 0.000 claims description 3
- 229910052763 palladium Inorganic materials 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
- RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 claims description 2
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- 206010013654 Drug abuse 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
- 235000011054 acetic acid Nutrition 0.000 claims description 2
- 206010001584 alcohol abuse Diseases 0.000 claims description 2
- 208000025746 alcohol use disease Diseases 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 230000007017 scission Effects 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- 238000006467 substitution reaction Methods 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
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 22
- 235000011167 hydrochloric acid Nutrition 0.000 claims 3
- 101100276531 Streptomyces halstedii sch4 gene Chemical group 0.000 claims 2
- RASCOYOTNOGKJJ-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohex-2-en-1-one;4-[(dimethylamino)methyl]-3-phenylcyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=CC=C1.COC1=CC=CC(C=2C(CCC(=O)C=2)CN(C)C)=C1 RASCOYOTNOGKJJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 206010011224 Cough Diseases 0.000 claims 1
- 101100073352 Streptomyces halstedii sch1 gene Proteins 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 208000023504 respiratory system disease Diseases 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 10
- 239000011541 reaction mixture Substances 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
- 125000004429 atom Chemical group 0.000 description 7
- 239000005051 trimethylchlorosilane Substances 0.000 description 7
- BXCBHDJKDXLFAF-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-3-(3-methoxyphenyl)cyclohex-2-en-1-one;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C(CCC(=O)C=2)CN(C)C)=C1 BXCBHDJKDXLFAF-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000012071 phase Substances 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
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 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
- 150000003254 radicals Chemical class 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 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 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000005764 inhibitory process Effects 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
- BFQUXINHKGBHLT-UHFFFAOYSA-N 3-(3,4-difluorophenyl)-4-[(dimethylamino)methyl]cyclohex-2-en-1-one Chemical compound CN(C)CC1CCC(=O)C=C1C1=CC=C(F)C(F)=C1 BFQUXINHKGBHLT-UHFFFAOYSA-N 0.000 description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10000311A DE10000311A1 (de) | 2000-01-05 | 2000-01-05 | Aminomethyl-Phonyl-Cyclohexanonderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20022338A3 true CZ20022338A3 (cs) | 2002-11-13 |
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| CZ20022338A CZ20022338A3 (cs) | 2000-01-05 | 2000-12-27 | Deriváty aminomethyl-fenyl-cyklohexanu, způsob jejich výroby, léčiva tyto látky obsahující a jejich pouľití |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| DE10326097A1 (de) * | 2003-06-06 | 2005-01-05 | Grünenthal GmbH | Verfahren zur Herstellung von Dimethyl-(3-aryl-butyl)-aminverbindungen |
| 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 |
| TWI496762B (zh) | 2006-07-24 | 2015-08-21 | 歌林達股份有限公司 | 製備（１ｒ，２ｒ）-３-（３-二甲胺基-１-乙基-２-甲基-丙基）-酚之方法 |
| JP5009736B2 (ja) * | 2007-10-15 | 2012-08-22 | 日本曹達株式会社 | 環状アミノエーテルを用いたマンニッヒ反応 |
| US7763754B2 (en) | 2008-02-29 | 2010-07-27 | Gruenenthal Gmbh | Process for producing (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexane-1,3-diol |
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| 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 |
| US3974157A (en) * | 1974-03-04 | 1976-08-10 | Pennwalt Corporation | 1-(Amino-alkyl)-2-aryl-cyclohexane alcohols and esters |
| JPS51143650A (en) * | 1975-06-06 | 1976-12-10 | Takeda Chem Ind Ltd | A process for preparing cyclohexanol derivatives |
| IL93610A0 (en) | 1989-03-08 | 1990-12-23 | Merck Sharp & Dohme | Tetrahydroquinoline derivatives,their preparation and pharmaceutical compositions containing them |
| IL112569A (en) * | 1994-02-10 | 1999-12-22 | Wyeth John & Brother Ltd | Pharmaceutical compositions comprising cyclohexylamine derivatives certain such novel compounds and their preparation |
| DE19525137C2 (de) | 1995-07-11 | 2003-02-27 | Gruenenthal Gmbh | 6-Dimethylaminomethyl-1-phenyl-cyclohexanverbin -dungen als Zwischenprodukte zur Herstellung pharmazeutischer Wirkstoffe |
| DE19547766A1 (de) * | 1995-12-20 | 1997-06-26 | Gruenenthal Gmbh | 1-Phenyl-2-dimethylaminomethyl-cyclohexan-1-ol-verbindungen als pharmazeutische Wirkstoffe |
| 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 |
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2000
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- 2000-12-27 AT AT00990824T patent/ATE280752T1/de active
- 2000-12-27 AU AU30169/01A patent/AU782862B2/en not_active Ceased
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2001
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- 2002-07-05 US US10/189,184 patent/US6890959B2/en not_active Expired - Fee Related
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