CA2197811C - Intermediaires dans le procede pour la preparation de derives de substitution en n de trifluoromethylphenyltetrahydropyridines - Google Patents

Intermediaires dans le procede pour la preparation de derives de substitution en n de trifluoromethylphenyltetrahydropyridines

Info

Publication number: CA2197811C
Authority: CA; Canada
Prior art keywords: formula; substituted; group; naphthyl; compounds
Prior art date: 1990-05-23
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 - Fee Related

Application number

CA002197811A

Other languages

English (en)

Other versions

CA2197811A1 (fr

Inventor

Umberto Guzzi

Costantino Palmieri

Tiziano Croci

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.)

Sanofi Aventis France

Original Assignee

Sanofi SA

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.)

1990-05-23

Filing date

1991-05-23

Publication date

1999-11-02

1990-05-23 Priority claimed from FR9006474A external-priority patent/FR2662442A1/fr

1991-05-23 Application filed by Sanofi SA filed Critical Sanofi SA

1991-11-24 Publication of CA2197811A1 publication Critical patent/CA2197811A1/fr

1999-11-02 Application granted granted Critical

1999-11-02 Publication of CA2197811C publication Critical patent/CA2197811C/fr

2011-05-23 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title abstract description 12
239000000543 intermediate Substances 0.000 title abstract description 6
238000000034 method Methods 0.000 title description 18
230000008569 process Effects 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 95
-1 N-substituted 4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridines Chemical class 0.000 claims abstract description 47
125000001624 naphthyl group Chemical group 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 23
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
150000007522 mineralic acids Chemical class 0.000 claims abstract description 8
150000007524 organic acids Chemical class 0.000 claims abstract description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
229910052500 inorganic mineral Inorganic materials 0.000 claims abstract description 6
239000011707 mineral Substances 0.000 claims abstract description 6
235000005985 organic acids Nutrition 0.000 claims abstract description 6
125000006383 alkylpyridyl group Chemical group 0.000 claims abstract description 4
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230000008991 intestinal motility Effects 0.000 abstract description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
239000000203 mixture Substances 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
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239000002253 acid Substances 0.000 description 23
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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238000006722 reduction reaction Methods 0.000 description 11
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IFYKRMQORZOMNY-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine Chemical class FC(F)(F)C1=CC=CC(C=2CCNCC=2)=C1 IFYKRMQORZOMNY-UHFFFAOYSA-N 0.000 description 9
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000002904 solvent Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
229910010084 LiAlH4 Inorganic materials 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
125000000217 alkyl group Chemical group 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000012280 lithium aluminium hydride Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
125000004356 hydroxy functional group Chemical group O* 0.000 description 7
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238000005727 Friedel-Crafts reaction Methods 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
125000002947 alkylene group Chemical group 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
239000012458 free base Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000007858 starting material Substances 0.000 description 6
150000001728 carbonyl compounds Chemical class 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
239000003814 drug Substances 0.000 description 5
230000029142 excretion Effects 0.000 description 5
230000002550 fecal effect Effects 0.000 description 5
238000001914 filtration Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
150000004678 hydrides Chemical class 0.000 description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
RJFISGALWPADNA-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine;hydrochloride Chemical compound Cl.FC(F)(F)C1=CC=CC(C=2CCNCC=2)=C1 RJFISGALWPADNA-UHFFFAOYSA-N 0.000 description 4
239000002841 Lewis acid Substances 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
150000001266 acyl halides Chemical class 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
125000001309 chloro group Chemical group Cl* 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
NARWYSCMDPLCIQ-UHFFFAOYSA-N ethane;hydrochloride Chemical compound Cl.CC NARWYSCMDPLCIQ-UHFFFAOYSA-N 0.000 description 4
210000003608 fece Anatomy 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
150000007517 lewis acids Chemical class 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
238000007911 parenteral administration 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
150000003254 radicals Chemical class 0.000 description 4
230000011514 reflex Effects 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
206010010774 Constipation Diseases 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
150000001263 acyl chlorides Chemical class 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
230000002891 anorexigenic effect Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000007810 chemical reaction solvent Substances 0.000 description 3
XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
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230000002035 prolonged effect Effects 0.000 description 3
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239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
238000003756 stirring Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000758 substrate Substances 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
MBERCTJMXDKBID-UHFFFAOYSA-N 1-(6,7-dimethoxynaphthalen-2-yl)ethanone Chemical compound C1=C(C(C)=O)C=C2C=C(OC)C(OC)=CC2=C1 MBERCTJMXDKBID-UHFFFAOYSA-N 0.000 description 2
CLQCQQYCHDTCEH-UHFFFAOYSA-N 1-phenyl-2-(trifluoromethyl)-3,4-dihydro-2h-pyridine Chemical class FC(F)(F)C1CCC=CN1C1=CC=CC=C1 CLQCQQYCHDTCEH-UHFFFAOYSA-N 0.000 description 2
OSKZYKATAHBWQX-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)acetic acid Chemical compound C1=C(CC(O)=O)C=C2C=C(OC)C(OC)=CC2=C1 OSKZYKATAHBWQX-UHFFFAOYSA-N 0.000 description 2
GWZFGRXOECUSMX-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)oxirane Chemical compound C1=C2C=C(OC)C(OC)=CC2=CC=C1C1CO1 GWZFGRXOECUSMX-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
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238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
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AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
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239000000654 additive Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
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125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000007809 chemical reaction catalyst Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
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238000009833 condensation Methods 0.000 description 2
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238000006482 condensation reaction Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000017858 demethylation Effects 0.000 description 2
238000010520 demethylation reaction Methods 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000004853 tetrahydropyridinyl group Chemical class N1(CCCC=C1)* 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
CVQMURYJMVLBGB-UHFFFAOYSA-N 1-[2-(6,7-dimethylnaphthalen-2-yl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine;hydrochloride Chemical compound Cl.C1=C2C=C(C)C(C)=CC2=CC=C1CCN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 CVQMURYJMVLBGB-UHFFFAOYSA-N 0.000 description 1
VVNCOLCABAUOOS-UHFFFAOYSA-N 1-[2-(6-methoxynaphthalen-2-yl)ethyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine;hydrochloride Chemical compound Cl.C1=CC2=CC(OC)=CC=C2C=C1CCN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 VVNCOLCABAUOOS-UHFFFAOYSA-N 0.000 description 1
UZZAVYVODPLGLU-UHFFFAOYSA-N 1-[2-(6-methoxynaphthalen-2-yl)propyl]-4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridine;hydrochloride Chemical compound Cl.C1=CC2=CC(OC)=CC=C2C=C1C(C)CN(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 UZZAVYVODPLGLU-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
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LOWWSYWGAKCKLG-UHFFFAOYSA-N 2-(6-methoxynaphthalen-1-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC2=CC(OC)=CC=C21 LOWWSYWGAKCKLG-UHFFFAOYSA-N 0.000 description 1
UEINDOPFSYNURD-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)-1-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]ethanone Chemical compound C1=CC2=CC(OC)=CC=C2C=C1CC(=O)N(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 UEINDOPFSYNURD-UHFFFAOYSA-N 0.000 description 1
YOTGFTTVZMMZQW-UHFFFAOYSA-N 2-(6-methoxynaphthalen-2-yl)-1-[4-[3-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]propan-1-one Chemical compound C1=CC2=CC(OC)=CC=C2C=C1C(C)C(=O)N(CC=1)CCC=1C1=CC=CC(C(F)(F)F)=C1 YOTGFTTVZMMZQW-UHFFFAOYSA-N 0.000 description 1
DVZRYTWXFWRYPT-UHFFFAOYSA-N 2-(oxiran-2-yl)pyridine Chemical compound C1OC1C1=CC=CC=N1 DVZRYTWXFWRYPT-UHFFFAOYSA-N 0.000 description 1
OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 description 1
WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
LTALBWXOVLYIMT-UHFFFAOYSA-N 2-bromo-1-(6,7-dimethoxynaphthalen-2-yl)ethanone Chemical compound C1=C(C(=O)CBr)C=C2C=C(OC)C(OC)=CC2=C1 LTALBWXOVLYIMT-UHFFFAOYSA-N 0.000 description 1
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239000007788 liquid Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000463 material Substances 0.000 description 1
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150000005217 methyl ethers Chemical class 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
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SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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239000003495 polar organic solvent Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
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230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
UMSVPCYSAUKCAZ-UHFFFAOYSA-N propane;hydrochloride Chemical compound Cl.CCC UMSVPCYSAUKCAZ-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
230000002633 protecting effect Effects 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000011002 quantification Methods 0.000 description 1
150000003333 secondary alcohols Chemical group 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
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235000019698 starch Nutrition 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
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239000000375 suspending agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
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229940095064 tartrate Drugs 0.000 description 1
150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
230000002936 tranquilizing effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Pyridine Compounds (AREA)

CA002197811A 1990-05-23 1991-05-23 Intermediaires dans le procede pour la preparation de derives de substitution en n de trifluoromethylphenyltetrahydropyridines Expired - Fee Related CA2197811C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9006474		1990-05-23
FR9006474A FR2662442A1 (fr)	1990-05-23	1990-05-23	Trifluoromethylphenyltetrahydropyridines n-substituees procede pour leur preparation, intermediaires du procede et compositions pharmaceutiques les contenant.
CA002043136A CA2043136C (fr)	1990-05-23	1991-05-23	Trifluoromethylphenyltetrahydropyridines, procede pour leur preparation, intermediaires dans ledit procede, et compositions pharmaceutiques qui les contiennent

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Application Number	Title	Priority Date	Filing Date
CA002043136A Division CA2043136C (fr)	1990-05-23	1991-05-23	Trifluoromethylphenyltetrahydropyridines, procede pour leur preparation, intermediaires dans ledit procede, et compositions pharmaceutiques qui les contiennent

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CA2197811A1 CA2197811A1 (fr)	1991-11-24
CA2197811C true CA2197811C (fr)	1999-11-02

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Publication	Publication Date	Title
AU633858B2 (en)	1993-02-11	Arylpiperidine derivatives
FI77448C (fi)	1989-03-10	Foerfarande foer framstaellning av terapeutiskt anvaendbara 1-fenyl-2-piperidinopropanolderivat.
CA1111850A (fr)	1981-11-03	Derives de la phtalazine ayant la propriete d'inhiber la phosphodiesterase et de stimuler de coeur
EP0170213B1 (fr)	1990-01-10	Agents à base de glutarimide ayant des propriétés anxiolytiques et antihypertensives
HU196058B (en)	1988-09-28	Process for producing new piperidine-methanol derivatives
CA2043136C (fr)	1998-03-10	Trifluoromethylphenyltetrahydropyridines, procede pour leur preparation, intermediaires dans ledit procede, et compositions pharmaceutiques qui les contiennent
US4021564A (en)	1977-05-03	Neuroleptic piperidine compounds
US5618822A (en)	1997-04-08	N-substituted trifluoromethylphenyltetrahydropyridines, process for the preparation thereof, intermediates in said process and pharmaceutical compositions containing them
IE780110L (en)	1978-08-03	Amides.
IE46442B1 (en)	1983-06-15	Morphine derivatives
US5541217A (en)	1996-07-30	4-arylcyclopenta[c]pyrrole analgesics
AU610492B2 (en)	1991-05-23	5-substituted octahydroindolizine analgesics compounds and 7-keto intermediates
WO1995025732A1 (fr)	1995-09-28	DERIVES N-p-HALOBENZOYLMETHYLE DE 4-(FLUOROPHENYL)-3-((3,4-(METHYLENEDIOXY)PHENOXY)METHYL)PIPERIDINE
HU192090B (en)	1987-05-28	Process for preparing new tetrazolyl derivatives and pharmaceutical compositions containing such compounds
FI78682C (fi)	1989-09-11	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara oximetrar.
US3178420A (en)	1965-04-13	Amino-2-hydroxy-1-propoxy benzal derivatives of fluorene and xanthene
HU184936B (en)	1984-11-28	Process for preparing piperidine derivatives of 4,5-dialkyl-3-hydroxy-pyrrole-2-carboxylic acid esters
JPS60109567A (ja)	1985-06-15	ビス（置換メチル）―メチル―イソキノリン誘導体
IE53189B1 (en)	1988-08-17	Benzoyl-phenyl-piperidine derivatives,method for their preparation and their therapeutic application
US5523412A (en)	1996-06-04	Intermediates for 4-arylcyclohepta[c]pyrrole analgesics
CA1066287A (fr)	1979-11-13	Produits a base de 4-benzoyl-4-hydroxypiperidine
US4321382A (en)	1982-03-23	2-Amino-11b-aryl-benzo[a]quinolizines
JPH04211059A (ja)	1992-08-03	新規なテトラヒドロピリジン誘導体
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