SK75498A3 - Processes and intermediates for preparing 1-benzyl-4-((5,6- -dimethoxy-1-indanon)-2-yl)methylpiperidine - Google Patents

Processes and intermediates for preparing 1-benzyl-4-((5,6- -dimethoxy-1-indanon)-2-yl)methylpiperidine Download PDF

Info

Publication number: SK75498A3
Authority: SK; Slovakia
Prior art keywords: alkyl; compound; formula; trifluoromethyl; alkoxy
Prior art date: 1995-12-15

Application number

SK754-98A

Other languages

English (en)

Slovak (sk)

Inventor

Keith M Devries

Original Assignee

Pfizer

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.)

1995-12-15

Filing date

1996-10-11

Publication date

1999-08-06

1996-10-11 Application filed by Pfizer filed Critical Pfizer

1999-08-06 Publication of SK75498A3 publication Critical patent/SK75498A3/sk

Links

238000000034 method Methods 0.000 title claims description 36
239000000543 intermediate Substances 0.000 title abstract description 5
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 91
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
239000002253 acid Substances 0.000 claims abstract description 18
125000001424 substituent group Chemical group 0.000 claims abstract description 18
-1 benzyl halide Chemical class 0.000 claims abstract description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims abstract description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 42
238000006243 chemical reaction Methods 0.000 claims description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
239000002904 solvent Substances 0.000 claims description 17
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
239000000203 mixture Substances 0.000 claims description 9
VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical group CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 claims description 9
239000002585 base Substances 0.000 claims description 8
239000003153 chemical reaction reagent Substances 0.000 claims description 7
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
239000012442 inert solvent Substances 0.000 claims description 5
239000003960 organic solvent Substances 0.000 claims description 5
101000650578 Salmonella phage P22 Regulatory protein C3 Proteins 0.000 claims description 3
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 3
101001040920 Triticum aestivum Alpha-amylase inhibitor 0.28 Proteins 0.000 claims description 3
239000003929 acidic solution Substances 0.000 claims description 3
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
239000012022 methylating agents‎ Substances 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 abstract description 7
238000004519 manufacturing process Methods 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 9
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 3
125000001475 halogen functional group Chemical group 0.000 abstract 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
238000004128 high performance liquid chromatography Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
150000003839 salts Chemical class 0.000 description 12
238000002360 preparation method Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000007787 solid Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 7
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
235000019439 ethyl acetate Nutrition 0.000 description 5
230000014759 maintenance of location Effects 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
IHMQOBPGHZFGLC-UHFFFAOYSA-N 5,6-dimethoxy-2,3-dihydroinden-1-one Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)CC2 IHMQOBPGHZFGLC-UHFFFAOYSA-N 0.000 description 3
208000024827 Alzheimer disease Diseases 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
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206010039966 Senile dementia Diseases 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000012458 free base Substances 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 3
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
ALXNSPKCYKUICH-UHFFFAOYSA-N 5,6-dimethoxy-2-(1-methylpiperidin-2-yl)-2,3-dihydroinden-1-one Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1C1CCCCN1C ALXNSPKCYKUICH-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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150000007513 acids Chemical class 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
235000019438 castor oil Nutrition 0.000 description 2
239000004359 castor oil Substances 0.000 description 2
208000026106 cerebrovascular disease Diseases 0.000 description 2
239000012043 crude product Substances 0.000 description 2
229910052805 deuterium Inorganic materials 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
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239000003755 preservative agent Substances 0.000 description 2
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239000006190 sub-lingual tablet Substances 0.000 description 2
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229940095064 tartrate Drugs 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
239000003039 volatile agent Substances 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-L 2-(carboxymethyl)-2-hydroxysuccinate Chemical compound [O-]C(=O)CC(O)(C(=O)O)CC([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-L 0.000 description 1
QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
AUYQMCCWFNSFGV-UHFFFAOYSA-N 3-piperidin-1-ium-4-ylpropanoate Chemical compound OC(=O)CCC1CCNCC1 AUYQMCCWFNSFGV-UHFFFAOYSA-N 0.000 description 1
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235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
238000002955 isolation Methods 0.000 description 1
229960003511 macrogol Drugs 0.000 description 1
235000009973 maize Nutrition 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical class C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229950008882 polysorbate Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000006403 short-term memory Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
UKKLUBWWAGMMAG-UHFFFAOYSA-N tris(2-hydroxyethyl)azanium;bromide Chemical compound Br.OCCN(CCO)CCO UKKLUBWWAGMMAG-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/30—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
- C07D211/32—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Hydrogenated Pyridines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)

SK754-98A 1995-12-15 1996-10-11 Processes and intermediates for preparing 1-benzyl-4-((5,6- -dimethoxy-1-indanon)-2-yl)methylpiperidine SK75498A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US875395P	1995-12-15	1995-12-15
PCT/IB1996/001076 WO1997022584A1 (fr)	1995-12-15	1996-10-11	Procedes de preparation de 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine et intermediaires utilises a cet effet

Publications (1)

Publication Number	Publication Date
SK75498A3 true SK75498A3 (en)	1999-08-06

Family

ID=21733469

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK754-98A SK75498A3 (en)	1995-12-15	1996-10-11	Processes and intermediates for preparing 1-benzyl-4-((5,6- -dimethoxy-1-indanon)-2-yl)methylpiperidine

Country Status (33)

Country	Link
EP (1)	EP0883607A1 (fr)
JP (1)	JP3066083B2 (fr)
KR (1)	KR20000064387A (fr)
AP (1)	AP708A (fr)
AR (1)	AR004368A1 (fr)
AU (1)	AU716462B2 (fr)
BG (1)	BG102525A (fr)
BR (1)	BR9612018A (fr)
CA (1)	CA2237647A1 (fr)
CO (1)	CO4750831A1 (fr)
CZ (1)	CZ180898A3 (fr)
DZ (1)	DZ2141A1 (fr)
GT (1)	GT199600092A (fr)
HN (1)	HN1996000065A (fr)
HR (1)	HRP960592A2 (fr)
HU (1)	HUP9904275A3 (fr)
IL (3)	IL136421A0 (fr)
IS (1)	IS4752A (fr)
MA (1)	MA24032A1 (fr)
NO (1)	NO982712L (fr)
NZ (1)	NZ318843A (fr)
OA (1)	OA10694A (fr)
PE (1)	PE25698A1 (fr)
PL (1)	PL197306B1 (fr)
RO (1)	RO121382B1 (fr)
RU (1)	RU2160731C2 (fr)
SK (1)	SK75498A3 (fr)
TN (1)	TNSN96153A1 (fr)
TW (1)	TW414787B (fr)
UY (1)	UY24401A1 (fr)
WO (1)	WO1997022584A1 (fr)
YU (1)	YU49486B (fr)
ZA (1)	ZA9610533B (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE292116T1 (de)	1998-01-16	2005-04-15	Eisai Co Ltd	Verfahren zur herstellung von donepezilderivaten
IL125809A (en)	1998-08-17	2005-08-31	Finetech Lab Ltd	Process and intermediates for production of donepezil and related compounds
US7148354B2 (en) *	2002-07-24	2006-12-12	Dr. Reddy's Laboratories Limited	Process for preparation of donepezil
IL150982A (en)	2002-07-30	2007-02-11	Ori Lerman	Process for making Donafzil
IL151253A0 (en) *	2002-08-14	2003-04-10	Finetech Lab Ltd	Process for production of highly pure donepezil hydrochloride
US6649765B1 (en)	2003-02-12	2003-11-18	Usv Limited, Bsd Marg.	Process for the preparation of 1-benzyl-4(5,6-dimethoxy-1-indanon)-2-yl) methyl piperidine hydrochloride (Donepezil HCL)
US6953856B2 (en)	2003-02-12	2005-10-11	Usv, Limited	Process for the preparation of 1-benzyl-4-(5,6-dimethoxy-1-indanon)-2-yl) methyl piperidine hydrochloride (Donepezil HCI)
EP1608371A1 (fr) *	2003-03-21	2005-12-28	Ranbaxy Laboratories, Ltd.	Procede de preparation de donepezil et de ses derives
WO2004099142A1 (fr) *	2003-05-05	2004-11-18	Ranbaxy Laboratories Limited	Sel de bromhydrate de benzyl-piperidylmethyl-indanone et ses polymorphes
US7446203B2 (en)	2003-07-01	2008-11-04	Hetero Drugs Limited	Preparation of intermediates for acetycholinesterase inhibitors
CN1280273C (zh)	2003-11-05	2006-10-18	天津和美生物技术有限公司	合成多奈哌齐及其衍生物的方法
WO2006035433A2 (fr)	2004-09-29	2006-04-06	Chemagis Ltd.	Utilisation de maleate de donepezil purifie pour preparer un hydrochlorure de donepezil amorphe pharmaceutiquement pur
CN100436416C (zh) *	2005-07-29	2008-11-26	西南合成制药股份有限公司	盐酸多奈哌齐合成工艺
GB0515803D0 (en) *	2005-07-30	2005-09-07	Pliva Hrvatska D O O	Intermediate compounds
AR057910A1 (es)	2005-11-18	2007-12-26	Synthon Bv	Proceso para preparar donepezilo
NZ569532A (en)	2006-01-04	2010-11-26	Cipla Ltd	Process and intermediate for preparation of donepezil
AU2007333586A1 (en)	2006-12-11	2008-06-19	Reviva Pharmaceuticals, Inc.	Compositions, synthesis, and methods of using indanone based cholinesterase inhibitors
WO2013078608A1 (fr)	2011-11-29	2013-06-06	Ziqiang Gu	Pamoate de donepezil et ses procédés de fabrication et d'utilisation
AU2014307803A1 (en)	2013-08-16	2016-03-10	Universiteit Maastricht	Treatment of cognitive impairment with PDE4 inhibitor

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FI95572C (fi) *	1987-06-22	1996-02-26	Eisai Co Ltd	Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi
FR2642069B1 (fr) *	1989-01-20	1991-04-12	Rhone Poulenc Sante	Nouveaux derives du benzopyranne, leur preparation et les compositions pharmaceutiques qui les contiennent
DE4439822A1 (de) *	1994-11-08	1996-08-29	Bayer Ag	Verfahren zur Herstellung von Benzyl-piperidylmethyl-indanonen

1996
- 1996-10-11 CZ CZ981808A patent/CZ180898A3/cs unknown
- 1996-10-11 NZ NZ318843A patent/NZ318843A/xx unknown
- 1996-10-11 HU HU9904275A patent/HUP9904275A3/hu unknown
- 1996-10-11 RU RU98111204/04A patent/RU2160731C2/ru not_active IP Right Cessation
- 1996-10-11 SK SK754-98A patent/SK75498A3/sk unknown
- 1996-10-11 EP EP96931937A patent/EP0883607A1/fr not_active Withdrawn
- 1996-10-11 AU AU70925/96A patent/AU716462B2/en not_active Ceased
- 1996-10-11 IL IL13642196A patent/IL136421A0/xx unknown
- 1996-10-11 WO PCT/IB1996/001076 patent/WO1997022584A1/fr not_active Ceased
- 1996-10-11 PL PL327512A patent/PL197306B1/pl not_active IP Right Cessation
- 1996-10-11 CA CA002237647A patent/CA2237647A1/fr not_active Abandoned
- 1996-10-11 RO RO98-01070A patent/RO121382B1/ro unknown
- 1996-10-11 IL IL12445296A patent/IL124452A0/xx unknown
- 1996-10-11 JP JP9522607A patent/JP3066083B2/ja not_active Expired - Lifetime
- 1996-10-11 BR BR9612018A patent/BR9612018A/pt not_active Application Discontinuation
- 1996-10-11 KR KR1019980704423A patent/KR20000064387A/ko not_active Ceased
- 1996-10-11 IL IL13642096A patent/IL136420A0/xx unknown
- 1996-10-14 TW TW085112515A patent/TW414787B/zh not_active IP Right Cessation
- 1996-10-15 HN HN1996000065A patent/HN1996000065A/es unknown
- 1996-11-18 GT GT199600092A patent/GT199600092A/es unknown
- 1996-12-09 PE PE1996000883A patent/PE25698A1/es not_active Application Discontinuation
- 1996-12-10 AR ARP960105577A patent/AR004368A1/es unknown
- 1996-12-11 DZ DZ960186A patent/DZ2141A1/fr active
- 1996-12-11 MA MA24424A patent/MA24032A1/fr unknown
- 1996-12-11 YU YU66096A patent/YU49486B/sh unknown
- 1996-12-11 TN TNTNSN96153A patent/TNSN96153A1/fr unknown
- 1996-12-12 UY UY24401A patent/UY24401A1/es not_active IP Right Cessation
- 1996-12-12 CO CO96065334A patent/CO4750831A1/es unknown
- 1996-12-12 AP APAP/P/1996/000892A patent/AP708A/en active
- 1996-12-13 ZA ZA9610533A patent/ZA9610533B/xx unknown
- 1996-12-13 HR HR60/008,753A patent/HRP960592A2/xx not_active Application Discontinuation
1998
- 1998-05-22 IS IS4752A patent/IS4752A/is unknown
- 1998-06-05 OA OA9800076A patent/OA10694A/en unknown
- 1998-06-09 BG BG102525A patent/BG102525A/xx unknown
- 1998-06-12 NO NO982712A patent/NO982712L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
AU7092596A (en)	1997-07-14
IL136421A0 (en)	2001-06-14
MX9804820A (es)	1998-10-31
NZ318843A (en)	2000-01-28
EP0883607A1 (fr)	1998-12-16
AP708A (en)	1998-12-04
OA10694A (en)	2001-05-04
NO982712D0 (no)	1998-06-12
JP3066083B2 (ja)	2000-07-17
CA2237647A1 (fr)	1997-06-26
HRP960592A2 (en)	1998-06-30
HUP9904275A2 (hu)	2000-05-28
PE25698A1 (es)	1998-05-21
IL124452A0 (en)	1998-12-06
CO4750831A1 (es)	1999-03-31
NO982712L (no)	1998-06-12
KR20000064387A (ko)	2000-11-06
MA24032A1 (fr)	1997-07-01
PL197306B1 (pl)	2008-03-31
HN1996000065A (es)	1997-06-26
YU66096A (en)	1999-11-22
ZA9610533B (en)	1998-06-15
AP9600892A0 (en)	1997-01-31
PL327512A1 (en)	1998-12-21
AR004368A1 (es)	1998-11-04
BG102525A (en)	1999-05-31
IL136420A0 (en)	2001-06-14
BR9612018A (pt)	1999-02-17
WO1997022584A1 (fr)	1997-06-26
HUP9904275A3 (en)	2001-05-28
CZ180898A3 (cs)	1999-05-12
JPH11500756A (ja)	1999-01-19
AU716462B2 (en)	2000-02-24
RU2160731C2 (ru)	2000-12-20
UY24401A1 (es)	1997-06-09
GT199600092A (es)	1998-05-12
IS4752A (is)	1998-05-22
TW414787B (en)	2000-12-11
DZ2141A1 (fr)	2002-07-23
RO121382B1 (ro)	2007-04-30
YU49486B (sh)	2006-08-17
TNSN96153A1 (fr)	2005-03-15

Publication	Publication Date	Title
SK75498A3 (en)	1999-08-06	Processes and intermediates for preparing 1-benzyl-4-((5,6- -dimethoxy-1-indanon)-2-yl)methylpiperidine
CA2516108C (fr)	2008-12-02	Polymorphes du chlorhydrate de donepezil et procede pour leur production
US5071859A (en)	1991-12-10	N-substituted azaheterocyclic carboxylic acids and pharmaceutical uses
SK283707B6 (sk)	2003-12-02	4-Aryl-1-fenylalkyl-1,2,3,6-tetrahydropyridínová zlúčenina, spôsob jej prípravy, medziprodukty a farmaceutický prostriedok obsahujúci túto zlúčeninu
US20030176693A1 (en)	2003-09-18	Diphenylalkylamine derivatives useful as opioid receptor agonists
US6194428B1 (en)	2001-02-27	Use of 5-substituted pyridine and hexahydroquinoline-3 carboxylic acid derivatives for treating diseases of the central nervous system
KR20210034082A (ko)	2021-03-29	2,6-디아미노 피리딘 화합물
US6355642B1 (en)	2002-03-12	Tetrahydrobenzindole compounds
US20080070789A1 (en)	2008-03-20	Process for making amlodipine, derivatives thereof, and precursors therefor
CZ51694A3 (en)	1994-10-19	Benzoxazine derivatives, process of their preparation and pharmaceutical composition in which said derivatives are comprised
CZ20031779A3 (cs)	2004-10-13	Způsob přípravy amlodipinuŹ jeho derivátů a jejich prekurzorů
SK11372001A3 (sk)	2001-12-03	Piperidínové a piperazínové deriváty ako inhibítory vzniku a'beta' fibríl
JP2001511799A (ja)	2001-08-14	オキシド−スクアレンシクラーゼ阻害剤として有用なヘテロ環式化合物
SK42299A3 (en)	1999-12-10	N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics
JPH037280A (ja)	1991-01-14	新規ベンゾチオピラニルアミン
SK287098B6 (sk)	2009-12-07	Deriváty fenyl- a pyridyl-tetrahydropyridínu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje, a použitie
CZ280931B6 (cs)	1996-05-15	Opticky aktivní karboxamidové deriváty, farmaceutický prostředek s analgetickým účinkem a prostředek s agonistickým účinkem vzhledem ke k-receptorům
MXPA98004820A (en)	1999-01-11	Procedures and intermediates for preparing 1-bencil-4 - ((5,6-dimetoxi-1-indanon) -2-il) metilpiperid
JP4324381B2 (ja)	2009-09-02	Ｔｎｆ活性を有するフェニル−およびピリジル−ピペリジン類
SK78799A3 (en)	1999-12-10	Diphenyl alkyl-tetrahydropyridines, process for their preparation, and pharmaceutical compositions containing them
NO166788B (no)	1991-05-27	Fremgangsmaate for fremstilling av terapeutisk aktive tetrahydrobenzofuro(2,3-c)-pyridiner.
US5608069A (en)	1997-03-04	1-substituted, 3-carboxylic acid piperidine derivatives
SA96170395B1 (ar)	2006-05-20	عمليات ومركبات وسطية لتحضير 1- بنزيل - 4 - ((5.6-ثنائي ميثوكسي -1- إندانون) -2- يل) ميثيل بيبريدين 1-benzy1-4-((5.6-dimethoxy -1-Indanon)-2-y1)methy1piperidine
JPH0859654A (ja)	1996-03-05	中枢神経系治療用薬剤としての６−アミノ−１，４−ジヒドロピリジン類の使用およびそれらの製造方法
MXPA01004289A (en)	2002-06-05	Process for the preparation of the mesylate salt trihydrate of 1-(4-hydroxyphenyl) -2-(4-hydroxy-4- phenylpiperidin -1-yl) -1-propanol and intermediates useful therefor