CA2181089C - Derives de la piperidine et methode de preparation - Google Patents

Derives de la piperidine et methode de preparation Download PDF

Info

Publication number: CA2181089C
Authority: CA; Canada
Prior art keywords: formula; compound; substantially pure; mixture; piperidine
Prior art date: 1993-06-24
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 - Lifetime

Application number

CA002181089A

Other languages

English (en)

Other versions

CA2181089A1 (fr

Inventor

Thomas E. D'ambra

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.)

Individual

Original Assignee

Albany Molecular Research Inc

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.)

1993-06-24

Filing date

1994-06-21

Publication date

2000-05-23

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25677908&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2181089(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1994-06-21 Application filed by Albany Molecular Research Inc filed Critical Albany Molecular Research Inc

1994-06-21 Priority claimed from CA002147126A external-priority patent/CA2147126C/fr

1994-12-25 Publication of CA2181089A1 publication Critical patent/CA2181089A1/fr

2000-05-23 Application granted granted Critical

2000-05-23 Publication of CA2181089C publication Critical patent/CA2181089C/fr

2014-06-21 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 30
150000003053 piperidines Chemical class 0.000 title claims description 21
238000004519 manufacturing process Methods 0.000 title description 3
-1 piperidine derivative compounds Chemical class 0.000 claims abstract description 62
125000000217 alkyl group Chemical group 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 20
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
229910052736 halogen Inorganic materials 0.000 claims abstract description 16
150000002367 halogens Chemical class 0.000 claims abstract description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
125000001424 substituent group Chemical group 0.000 claims abstract description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
239000000203 mixture Substances 0.000 claims description 51
150000001875 compounds Chemical class 0.000 claims description 42
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 16
150000003839 salts Chemical class 0.000 claims description 14
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
239000007858 starting material Substances 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 6
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
239000011777 magnesium Substances 0.000 claims description 4
229910052749 magnesium Inorganic materials 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052744 lithium Inorganic materials 0.000 claims description 3
125000002524 organometallic group Chemical group 0.000 claims description 3
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
230000003266 anti-allergic effect Effects 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims 2
206010020751 Hypersensitivity Diseases 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
239000002904 solvent Substances 0.000 description 34
235000019439 ethyl acetate Nutrition 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
239000000243 solution Substances 0.000 description 26
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
239000007787 solid Substances 0.000 description 14
239000002585 base Substances 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
125000000468 ketone group Chemical group 0.000 description 12
238000010992 reflux Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
238000005804 alkylation reaction Methods 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
229960000351 terfenadine Drugs 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
150000007529 inorganic bases Chemical class 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000000047 product Substances 0.000 description 6
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
239000004215 Carbon black (E152) Substances 0.000 description 5
238000005917 acylation reaction Methods 0.000 description 5
239000005456 alcohol based solvent Substances 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
229930195733 hydrocarbon Natural products 0.000 description 5
150000002430 hydrocarbons Chemical class 0.000 description 5
239000010410 layer Substances 0.000 description 5
229920002261 Corn starch Polymers 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
239000000739 antihistaminic agent Substances 0.000 description 4
KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 4
KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 4
239000008120 corn starch Substances 0.000 description 4
229940099112 cornstarch Drugs 0.000 description 4
239000012043 crude product Substances 0.000 description 4
238000001640 fractional crystallisation Methods 0.000 description 4
150000008282 halocarbons Chemical class 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
YYEROYLAYAVZNW-UHFFFAOYSA-N 2-methyl-2-phenylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC=CC=C1 YYEROYLAYAVZNW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
238000005727 Friedel-Crafts reaction Methods 0.000 description 3
239000002841 Lewis acid Substances 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
230000010933 acylation Effects 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
230000001387 anti-histamine Effects 0.000 description 3
229940124630 bronchodilator Drugs 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
239000005453 ketone based solvent Substances 0.000 description 3
150000007517 lewis acids Chemical group 0.000 description 3
239000007788 liquid Substances 0.000 description 3
ZEUXAIYYDDCIRX-UHFFFAOYSA-N losartan carboxylic acid Chemical compound CCCCC1=NC(Cl)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1 ZEUXAIYYDDCIRX-UHFFFAOYSA-N 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
101150065749 Churc1 gene Proteins 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
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 2
208000028257 Joubert syndrome with oculorenal defect Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000000043 antiallergic agent Substances 0.000 description 2
229940125715 antihistaminic agent Drugs 0.000 description 2
238000007080 aromatic substitution reaction Methods 0.000 description 2
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical class C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
239000000168 bronchodilator agent Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000010531 catalytic reduction reaction Methods 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
229960004132 diethyl ether Drugs 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
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235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
150000002431 hydrogen Chemical class 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000000314 lubricant Substances 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
239000000463 material Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
210000004400 mucous membrane Anatomy 0.000 description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
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Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002181089A 1993-06-24 1994-06-21 Derives de la piperidine et methode de preparation Expired - Lifetime CA2181089C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US8310293A	1993-06-24	1993-06-24
US08/083,102		1993-06-24
CA002147126A CA2147126C (fr)	1993-06-24	1994-06-21	Derives de la piperidine et methode de preparation

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002147126A Division CA2147126C (fr)	1993-06-24	1994-06-21	Derives de la piperidine et methode de preparation

Publications (2)

Publication Number	Publication Date
CA2181089A1 CA2181089A1 (fr)	1994-12-25
CA2181089C true CA2181089C (fr)	2000-05-23

Family

ID=25677908

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA002254506A Expired - Lifetime CA2254506C (fr)	1993-06-24	1994-06-21	Derives de la piperidine et methode de preparation
CA002181089A Expired - Lifetime CA2181089C (fr)	1993-06-24	1994-06-21	Derives de la piperidine et methode de preparation

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
CA002254506A Expired - Lifetime CA2254506C (fr)	1993-06-24	1994-06-21	Derives de la piperidine et methode de preparation

Country Status (1)

Country	Link
CA (2)	CA2254506C (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2585705C (fr)	1994-05-18	2012-04-17	Aventis Pharmaceuticals Inc.	Methodes pour preparer des formes anhydres et hydratees de derives antihistaminiques de la piperidine; leurs formes polymorphes et pseudomorphes

1994
- 1994-06-21 CA CA002254506A patent/CA2254506C/fr not_active Expired - Lifetime
- 1994-06-21 CA CA002181089A patent/CA2181089C/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CA2254506A1 (fr)	1995-01-05
CA2181089A1 (fr)	1994-12-25
CA2254506C (fr)	2000-11-28

Legal Events

Date	Code	Title	Description
1996-07-12	EEER	Examination request
2014-08-25	MKEX	Expiry	Effective date: 20140623

Publication	Publication Date	Title
CA2147126C (fr)	1999-08-24	Derives de la piperidine et methode de preparation
CA2240735C (fr)	2006-08-29	Procede de preparation de derives de piperidine
CA2240927C (fr)	2006-08-22	Processus de production de derives de piperidine
US6797826B2 (en)	2004-09-28	Piperidine derivatives and process for their production
CA2181089C (fr)	2000-05-23	Derives de la piperidine et methode de preparation
AU729549B2 (en)	2001-02-01	Piperidine derivatives and process for their production
AU699799B2 (en)	1998-12-17	Piperidine derivatives and process for their production
HK1062672A (en)	2004-11-19	Process for preparing compounds useful as intermediates
NZ286116A (en)	1997-03-24	Substantially pure diphenylmethyl piperidin-1-yl substituted dimethylphenylacetic acid and esters; pharmaceutical compositions