DD294484A5 - Verfahren zur herstellung von 2-piperidinoalkanol-derivaten - Google Patents

Verfahren zur herstellung von 2-piperidinoalkanol-derivaten Download PDF

Info

Publication number: DD294484A5
Authority: DD; German Democratic Republic
Prior art keywords: mmol; ethyl acetate; title product; product; nmr
Prior art date: 1989-05-17

Application number

DD90340728A

Other languages

German (de)

English (en)

Inventor

Bertrand L Chenard

Original Assignee

Pfizer Inc.,Us

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.)

1989-05-17

Filing date

1990-05-16

Publication date

1991-10-02

1989-05-17 Priority claimed from PCT/US1989/002176 external-priority patent/WO1990014087A1/fr

1990-05-16 Application filed by Pfizer Inc.,Us filed Critical Pfizer Inc.,Us

1991-10-02 Publication of DD294484A5 publication Critical patent/DD294484A5/de

Links

238000004519 manufacturing process Methods 0.000 title abstract description 4
238000000034 method Methods 0.000 claims abstract description 54
150000001875 compounds Chemical class 0.000 claims abstract description 38
238000002360 preparation method Methods 0.000 claims abstract description 28
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims abstract description 6
125000003342 alkenyl group Chemical group 0.000 claims abstract 2
125000000304 alkynyl group Chemical group 0.000 claims abstract 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
229910052727 yttrium Inorganic materials 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 7
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 claims description 2
150000004678 hydrides Chemical class 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 12
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract description 7
239000008194 pharmaceutical composition Substances 0.000 abstract description 4
208000015114 central nervous system disease Diseases 0.000 abstract description 2
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 abstract 1
101150065749 Churc1 gene Proteins 0.000 abstract 1
239000004593 Epoxy Substances 0.000 abstract 1
102100038239 Protein Churchill Human genes 0.000 abstract 1
125000003710 aryl alkyl group Chemical group 0.000 abstract 1
125000003118 aryl group Chemical group 0.000 abstract 1
125000000958 aryl methylene group Chemical group 0.000 abstract 1
125000005110 aryl thio group Chemical group 0.000 abstract 1
125000004104 aryloxy group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 186
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 135
239000000047 product Substances 0.000 description 124
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
238000005481 NMR spectroscopy Methods 0.000 description 50
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
-1 4-hydroxy-4-tolylpiperazino Chemical group 0.000 description 47
239000000203 mixture Substances 0.000 description 41
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
239000007787 solid Substances 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
239000000243 solution Substances 0.000 description 20
238000010828 elution Methods 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 17
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
238000003818 flash chromatography Methods 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 13
239000012267 brine Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 12
150000002576 ketones Chemical class 0.000 description 11
238000010992 reflux Methods 0.000 description 10
239000005909 Kieselgur Substances 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000012442 inert solvent Substances 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
229910052794 bromium Inorganic materials 0.000 description 6
230000000324 neuroprotective effect Effects 0.000 description 6
150000002924 oxiranes Chemical class 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
230000002253 anti-ischaemic effect Effects 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000010410 layer Substances 0.000 description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
230000000269 nucleophilic effect Effects 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
238000005406 washing Methods 0.000 description 4
208000024827 Alzheimer disease Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
229910010082 LiAlH Inorganic materials 0.000 description 3
HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 3
208000018737 Parkinson disease Diseases 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
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238000001704 evaporation Methods 0.000 description 3
230000002461 excitatory amino acid Effects 0.000 description 3
239000003257 excitatory amino acid Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
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238000000526 short-path distillation Methods 0.000 description 3
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000001665 trituration Methods 0.000 description 3
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KJZBZOFESQSBCV-UHFFFAOYSA-N 4-benzylpiperidin-4-ol Chemical compound C=1C=CC=CC=1CC1(O)CCNCC1 KJZBZOFESQSBCV-UHFFFAOYSA-N 0.000 description 2
KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 2
DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 description 2
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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102000018899 Glutamate Receptors Human genes 0.000 description 2
108010027915 Glutamate Receptors Proteins 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
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235000019502 Orange oil Nutrition 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
230000003276 anti-hypertensive effect Effects 0.000 description 2
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239000002585 base Substances 0.000 description 2
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230000000903 blocking effect Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
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125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
230000003412 degenerative effect Effects 0.000 description 2
201000010099 disease Diseases 0.000 description 2
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238000006735 epoxidation reaction Methods 0.000 description 2
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238000001640 fractional crystallisation Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
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KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
150000004682 monohydrates Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 2
238000005191 phase separation Methods 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000843 powder Substances 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
238000000746 purification Methods 0.000 description 2
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
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238000003786 synthesis reaction Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
XGUPAUDEUUVJJO-UHFFFAOYSA-N 1-(2-hydroxy-2-thiophen-2-ylethyl)-4-phenylpiperidin-4-ol Chemical compound C=1C=CSC=1C(O)CN(CC1)CCC1(O)C1=CC=CC=C1 XGUPAUDEUUVJJO-UHFFFAOYSA-N 0.000 description 1
BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 1
PSDSORRYQPTKSV-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanol Chemical compound CC(O)C1=CC=C(F)C=C1 PSDSORRYQPTKSV-UHFFFAOYSA-N 0.000 description 1
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QIJNVLLXIIPXQT-UHFFFAOYSA-N 1-(4-fluorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(F)C=C1 QIJNVLLXIIPXQT-UHFFFAOYSA-N 0.000 description 1
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JLRNTPVSALEDDX-GOSISDBHSA-N 1-[(2s)-2-(4-chlorophenyl)-2-hydroxyethyl]-4-phenylpiperidin-4-ol Chemical compound C([C@@H](O)C=1C=CC(Cl)=CC=1)N(CC1)CCC1(O)C1=CC=CC=C1 JLRNTPVSALEDDX-GOSISDBHSA-N 0.000 description 1
CBXGLNWPAKZNTA-UHFFFAOYSA-N 1-[2-(4-aminophenyl)-2-hydroxyethyl]-4-phenylpiperidin-4-ol Chemical compound C1=CC(N)=CC=C1C(O)CN1CCC(O)(C=2C=CC=CC=2)CC1 CBXGLNWPAKZNTA-UHFFFAOYSA-N 0.000 description 1
JLRNTPVSALEDDX-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-hydroxyethyl]-4-phenylpiperidin-4-ol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1(O)C1=CC=CC=C1 JLRNTPVSALEDDX-UHFFFAOYSA-N 0.000 description 1
UGTNEQVDTRSDLY-UHFFFAOYSA-N 1-[2-hydroxy-2-[4-(trifluoromethyl)phenyl]ethyl]-4-phenylpiperidin-4-ol Chemical compound C=1C=C(C(F)(F)F)C=CC=1C(O)CN(CC1)CCC1(O)C1=CC=CC=C1 UGTNEQVDTRSDLY-UHFFFAOYSA-N 0.000 description 1
AWIDEBQUIJCLOC-UHFFFAOYSA-N 1-[4-tri(propan-2-yl)silyloxyphenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(O[Si](C(C)C)(C(C)C)C(C)C)C=C1 AWIDEBQUIJCLOC-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
VQEZTJFLXZGZHZ-UHFFFAOYSA-N 2,2,2-trichloroethyl 3-benzylidene-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound ClC(Cl)(Cl)COC(=O)N1C(C2)CCC1CC2=CC1=CC=CC=C1 VQEZTJFLXZGZHZ-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
IDLUMBHZGJYDAZ-UHFFFAOYSA-N 2-(4-benzyl-4-hydroxypiperidin-1-yl)-1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)C(C)N(CC1)CCC1(O)CC1=CC=CC=C1 IDLUMBHZGJYDAZ-UHFFFAOYSA-N 0.000 description 1
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238000007327 hydrogenolysis reaction Methods 0.000 description 1
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235000019796 monopotassium phosphate Nutrition 0.000 description 1
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125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
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229910000027 potassium carbonate Inorganic materials 0.000 description 1
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230000000506 psychotropic effect Effects 0.000 description 1
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KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
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ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
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238000002604 ultrasonography Methods 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/54—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

DD90340728A 1989-05-17 1990-05-16 Verfahren zur herstellung von 2-piperidinoalkanol-derivaten DD294484A5 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
PCT/US1989/002176 WO1990014087A1 (fr)	1989-05-17	1989-05-17	Derives de 2-piperidino-1-alcanol en tant qu'agents antiischemiques
PCT/US1990/000292 WO1990014088A1 (fr)	1989-05-17	1990-01-16	Derives de 2-piperidino-1-alcanol comme agents anti-ischemiques

Publications (1)

Publication Number	Publication Date
DD294484A5 true DD294484A5 (de)	1991-10-02

Family

ID=26779691

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD90340728A DD294484A5 (de)	1989-05-17	1990-05-16	Verfahren zur herstellung von 2-piperidinoalkanol-derivaten

Country Status (9)

Country	Link
EP (1)	EP0398578B1 (fr)
AU (1)	AU618191B2 (fr)
CA (1)	CA2016860C (fr)
DD (1)	DD294484A5 (fr)
ES (1)	ES2098248T3 (fr)
GR (1)	GR3023314T3 (fr)
NZ (1)	NZ233685A (fr)
PT (1)	PT94045B (fr)
YU (1)	YU47559B (fr)

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EP0554247B1 (fr) *	1990-05-10	2000-04-26	Pfizer Inc.	Indolone neuroprotecteur et derives apparentes
AU655840B2 (en) *	1991-07-17	1995-01-12	Pfizer Inc.	2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents
US6255322B1 (en)	1992-06-19	2001-07-03	Pfizer Inc.	2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents
PL173618B1 (pl) *	1992-10-30	1998-04-30	Pfizer	Związki 6-[2-(4-hydroksy-4-fenylopiperydyno)-1-hydroksypropylo]-3,4-dihydro-2(1H)-chinolonowe
AU672644B2 (en) *	1992-12-23	1996-10-10	Neurosearch A/S	Aryl substituted heterocyclic compounds
AU672052B2 (en) *	1992-12-23	1996-09-19	Neurosearch A/S	Antidepressant and antiparkinsonian compounds
AU671163B2 (en) *	1992-12-23	1996-08-15	Neurosearch A/S	Alkyl substituted heterocyclic compounds
TW281670B (fr) *	1993-09-02	1996-07-21	Hoffmann La Roche
RU2139857C1 (ru) *	1994-08-18	1999-10-20	Пфайзер Инк.	Производные 3-(пиперидинил-1)-хроман-4,7-диола и 1-(4-гидроксифенил)-2-(пиперидинил-1)-алканола, фармацевтическая композиция и способ связывания nmda рецептора
GB9510459D0 (en)	1995-05-24	1995-07-19	Zeneca Ltd	Bicyclic amines
FR2736053B1 (fr) *	1995-06-28	1997-09-19	Sanofi Sa	Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines
ZA9610741B (en)	1995-12-22	1997-06-24	Warner Lambert Co	4-Substituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610736B (en)	1995-12-22	1997-06-27	Warner Lambert Co	2-Substituted piperidine analogs and their use as subtypeselective nmda receptor antagonists
ZA9610745B (en) *	1995-12-22	1997-06-24	Warner Lambert Co	4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists
ZA9610738B (en)	1995-12-22	1997-06-24	Warner Lambert Co	Subtype selective nmda receptor ligands and the use thereof
BR9708947A (pt) *	1996-05-13	1999-08-03	Zeneca Ltd	Composto composição inseticida acaricida e nematicida método para combate e controle de pragas e processo para preparação de um composto
GB9623944D0 (en) *	1996-11-15	1997-01-08	Zeneca Ltd	Bicyclic amine derivatives
GB9624114D0 (en) *	1996-11-20	1997-01-08	Zeneca Ltd	Pesticidal bicyclic amine derivatives
GB9624611D0 (en) *	1996-11-26	1997-01-15	Zeneca Ltd	Bicyclic amine compounds
TW370451B (en)	1996-11-26	1999-09-21	Zeneca Ltd	Bicyclic amine derivatives
EP1472248A1 (fr)	2002-01-17	2004-11-03	Eli Lilly And Company	Modulateurs de recepteurs de l'acetylcholine

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3045688A1 (de) *	1980-12-04	1982-07-08	C.H. Boehringer Sohn, 6507 Ingelheim	Neue 8-arylalkyl-3-phenyl-3-nortropanole, deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zu ihrer herstellung
EP0076089A3 (fr) *	1981-09-28	1983-05-25	Beecham Group Plc	Dérivés azabicycloalkyles, leur procédé de préparation, et compositions pharmaceutiques les contenant
US4366154A (en) *	1981-11-09	1982-12-28	Sandoz, Inc.	Tropyl derivatives

1990
- 1990-05-09 EP EP19900304975 patent/EP0398578B1/fr not_active Expired - Lifetime
- 1990-05-09 ES ES90304975T patent/ES2098248T3/es not_active Expired - Lifetime
- 1990-05-15 CA CA002016860A patent/CA2016860C/fr not_active Expired - Lifetime
- 1990-05-15 PT PT94045A patent/PT94045B/pt not_active IP Right Cessation
- 1990-05-15 NZ NZ233685A patent/NZ233685A/en unknown
- 1990-05-16 AU AU55125/90A patent/AU618191B2/en not_active Ceased
- 1990-05-16 YU YU95890A patent/YU47559B/sh unknown
- 1990-05-16 DD DD90340728A patent/DD294484A5/de unknown
1997
- 1997-05-02 GR GR970400971T patent/GR3023314T3/el unknown

Also Published As

Publication number	Publication date
EP0398578A3 (fr)	1991-12-11
EP0398578B1 (fr)	1997-03-12
ES2098248T3 (es)	1997-05-01
CA2016860C (fr)	1998-07-28
NZ233685A (en)	1992-10-28
PT94045B (pt)	1996-12-31
YU95890A (en)	1992-05-28
GR3023314T3 (en)	1997-08-29
CA2016860A1 (fr)	1990-11-17
PT94045A (pt)	1991-01-08
AU5512590A (en)	1990-11-22
AU618191B2 (en)	1991-12-12
YU47559B (sh)	1995-10-03
EP0398578A2 (fr)	1990-11-22

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DE69030134T2 (de)	1997-06-19	2-Piperidino-1-alkanol-Derivate als antiischemische Wirkstoffe
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DE60102581T2 (de)	2005-02-03	Azabizyklische carbamate und ihre anwendung als antagonisten des alpha-7 nikotinischen acetylcholin rezeptors
EP0418716B1 (fr)	1994-04-06	Esters aminoalcohol d'acide thienylcarboxyliques leurs produits quaternaires, leur préparation et l'utilisation de ces composés
DE69224196T2 (de)	1998-05-20	3-aminopiperidine derivate und verwandete stickstoff enthaltende heterocyclische verbindungen
DE69413822T2 (de)	1999-02-25	Benzyloxychinuclidine als substanz p antagonisten
EP1487834B1 (fr)	2007-04-25	N-biarylamides aza-bicycliques ayant une affinite au recepteur d'acetyle-choline alpha7 nicotinique
AU618191B2 (en)	1991-12-12	2-cyclo-azo-1-alkanol derivatives as antiischemic agents
DE69102893T4 (de)	1995-08-10	Nervenschützende 3-Piperidino-4-Hydroxychromanderivate.
US5272160A (en)	1993-12-21	2-piperidino-1-alkanol derivatives as antiischemic agents
DE69133295T2 (de)	2004-03-18	3,9-diazabicyclo-[3.3.1]-nonanylderivate, verfahren und intermediate für ihre darstellung und sie enthaltende pharmazeutische zusammensetzungen
DE69102889T2 (de)	1994-11-03	Chirurgische Nähnadel, Verfahren und Gerät zum Schleifen von chirurgischen Nähnadeln.
DE69205312T2 (de)	1996-03-14	Substituierte Imidazol-2-one Derivate und Verfahren zu deren Herstellung.
DE9290042U1 (de)	1993-12-16	Pro-Arzneimittelester von phenolischen 2-Piperidino-1-alkanolen
DE3687515T2 (de)	1993-05-13	Oxa-, thia- und diazabicycloalkanderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel.
US5527912A (en)	1996-06-18	Intermediates for 2-piperidino-1-alkanol derivatives
NZ241346A (en)	1992-10-28	Phenyl- or thienyl-substituted 8-azabicyclo (3,2,1) octane; use as neuroprotective agents
DE4139143A1 (de)	1993-06-03	Neue benzochinoxaline, ihre herstellung und verwendung