CA2510750A1 - A process for preparing duloxetine and intermediates for use therein - Google Patents
A process for preparing duloxetine and intermediates for use therein Download PDFInfo
- Publication number
- CA2510750A1 CA2510750A1 CA002510750A CA2510750A CA2510750A1 CA 2510750 A1 CA2510750 A1 CA 2510750A1 CA 002510750 A CA002510750 A CA 002510750A CA 2510750 A CA2510750 A CA 2510750A CA 2510750 A1 CA2510750 A1 CA 2510750A1
- Authority
- CA
- Canada
- Prior art keywords
- duloxetine
- acid
- addition salt
- acid addition
- process according
- Prior art date
- 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.)
- Abandoned
Links
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 title claims abstract description 31
- 229960002866 duloxetine Drugs 0.000 title claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- 239000000543 intermediate Substances 0.000 title description 27
- ZEUITGRIYCTCEM-UHFFFAOYSA-N duloxetine Chemical compound C=1C=CC2=CC=CC=C2C=1OC(CCNC)C1=CC=CS1 ZEUITGRIYCTCEM-UHFFFAOYSA-N 0.000 claims abstract description 83
- 239000002253 acid Substances 0.000 claims abstract description 70
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 238000000034 method Methods 0.000 claims abstract description 61
- ZEUITGRIYCTCEM-QGZVFWFLSA-N (R)-duloxetine Chemical compound C1([C@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-QGZVFWFLSA-N 0.000 claims abstract description 22
- 239000002585 base Substances 0.000 claims abstract description 18
- 239000012458 free base Substances 0.000 claims abstract description 10
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 25
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- HZBOQOXQPRQKTF-UHFFFAOYSA-N bis(4-methylphenyl) 2,3-dihydroxybutanedioate Chemical compound C1=CC(C)=CC=C1OC(=O)C(O)C(O)C(=O)OC1=CC=C(C)C=C1 HZBOQOXQPRQKTF-UHFFFAOYSA-N 0.000 claims description 13
- NSFIAKFOCAEBER-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-UHFFFAOYSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkali metal bicarbonate Chemical class 0.000 claims description 8
- 230000001335 demethylating effect Effects 0.000 claims description 8
- 229960002496 duloxetine hydrochloride Drugs 0.000 claims description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- 235000006408 oxalic acid Nutrition 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- 239000012452 mother liquor Substances 0.000 claims description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229940095064 tartrate Drugs 0.000 claims description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 2
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 claims description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims description 2
- 150000003983 crown ethers Chemical class 0.000 claims description 2
- NTBIYBAYFBNTCD-UHFFFAOYSA-N dibenzoyl 2,3-dihydroxybutanedioate Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C(O)C(O)C(=O)OC(=O)C1=CC=CC=C1 NTBIYBAYFBNTCD-UHFFFAOYSA-N 0.000 claims description 2
- 229960002510 mandelic acid Drugs 0.000 claims description 2
- 150000003891 oxalate salts Chemical class 0.000 claims description 2
- 150000004714 phosphonium salts Chemical class 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 238000010934 O-alkylation reaction Methods 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 3
- 125000006308 propyl amino group Chemical group 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- CWLKTJOTWITYSI-UHFFFAOYSA-N 1-fluoronaphthalene Chemical compound C1=CC=C2C(F)=CC=CC2=C1 CWLKTJOTWITYSI-UHFFFAOYSA-N 0.000 description 2
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- WYMDDFRYORANCC-UHFFFAOYSA-N 2-[[3-[bis(carboxymethyl)amino]-2-hydroxypropyl]-(carboxymethyl)amino]acetic acid Chemical class OC(=O)CN(CC(O)=O)CC(O)CN(CC(O)=O)CC(O)=O WYMDDFRYORANCC-UHFFFAOYSA-N 0.000 description 1
- CUGBKQGQESIBMN-UHFFFAOYSA-N 3-thiophen-2-ylpropan-1-amine Chemical compound NCCCC1=CC=CS1 CUGBKQGQESIBMN-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
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- 229910019142 PO4 Inorganic materials 0.000 description 1
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- 230000001430 anti-depressive effect Effects 0.000 description 1
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- 125000005341 metaphosphate group Chemical group 0.000 description 1
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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- 230000000063 preceeding effect Effects 0.000 description 1
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- 239000003586 protic polar solvent Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
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- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229940071104 xylenesulfonate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0229583.0 | 2002-12-19 | ||
| GBGB0229583.0A GB0229583D0 (en) | 2002-12-19 | 2002-12-19 | A process for preparing duloxetine and intermediates for use therein |
| PCT/GB2003/005357 WO2004056795A1 (en) | 2002-12-19 | 2003-12-10 | A process for preparing duloxetine and intermediates for use therein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2510750A1 true CA2510750A1 (en) | 2004-07-08 |
Family
ID=9949985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002510750A Abandoned CA2510750A1 (en) | 2002-12-19 | 2003-12-10 | A process for preparing duloxetine and intermediates for use therein |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7645890B2 (https=) |
| EP (2) | EP1587801B1 (https=) |
| JP (1) | JP5259048B2 (https=) |
| KR (1) | KR100926723B1 (https=) |
| CN (2) | CN101125848B (https=) |
| AT (1) | ATE353081T1 (https=) |
| AU (2) | AU2003292396B2 (https=) |
| BR (1) | BR0316902A (https=) |
| CA (1) | CA2510750A1 (https=) |
| DE (1) | DE60311599T2 (https=) |
| ES (1) | ES2279971T3 (https=) |
| GB (1) | GB0229583D0 (https=) |
| HR (1) | HRP20050657A2 (https=) |
| IL (1) | IL169232A (https=) |
| IS (1) | IS7915A (https=) |
| MA (1) | MA27706A1 (https=) |
| MX (1) | MXPA05006659A (https=) |
| NZ (2) | NZ569874A (https=) |
| PL (1) | PL377380A1 (https=) |
| PT (1) | PT1587801E (https=) |
| RU (1) | RU2351594C2 (https=) |
| TN (1) | TNSN05167A1 (https=) |
| WO (1) | WO2004056795A1 (https=) |
| ZA (1) | ZA200505656B (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7550605B2 (en) * | 2004-08-05 | 2009-06-23 | Sun Pharmaceutical Industries Ltd. | Process for preparation of an anitdepressant compound |
| CZ297560B6 (cs) | 2004-10-26 | 2007-02-07 | Zentiva, A. S. | Zpusob výroby hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu (duloxetinu) |
| TWI306858B (en) * | 2004-12-23 | 2009-03-01 | Teva Pharma | Process for preparing pharmaceutically acceptable salts of duloxetine and intermediates thereof |
| EP1776049A2 (en) * | 2005-01-27 | 2007-04-25 | Teva Pharmaceutical Industries Ltd. | Duloxetine hcl polymorphs |
| WO2006096809A1 (en) | 2005-03-08 | 2006-09-14 | Teva Pharmaceutical Industries Ltd. | Crystal forms of (s)-(+)-n,n-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl) propanamine oxalate and the preparation thereof |
| TW200639162A (en) * | 2005-03-14 | 2006-11-16 | Teva Pharma | Pure duloxetine hydrochloride |
| US8093408B2 (en) * | 2005-06-21 | 2012-01-10 | The Company Wockhardt | Antidepressant oral pharmaceutical compositions |
| US8153824B2 (en) * | 2005-06-22 | 2012-04-10 | The Wockhardt Company | Antidepressant oral liquid compositions |
| WO2007038253A2 (en) * | 2005-09-22 | 2007-04-05 | Teva Pharmaceutical Industries Ltd. | Dnt-maleate and methods of preparation thereof |
| EP1863782A1 (en) * | 2005-12-05 | 2007-12-12 | Teva Pharmaceutical Industries Ltd. | 2-(n-methyl-propanamine)-3-(2-naphtol) thiophene, an imputity of duloxetine hydrochloride |
| EP1971593A2 (en) * | 2005-12-12 | 2008-09-24 | Medichem, S.A. | Improved synthesis and preparations of duloxetine salts |
| CZ299270B6 (cs) * | 2006-01-04 | 2008-06-04 | Zentiva, A. S. | Zpusob výroby hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu |
| EP1976844A4 (en) * | 2006-01-06 | 2010-11-03 | Msn Lab Ltd | IMPROVED METHOD FOR PURE DULOXETIN HYDROCHLORIDE |
| US7538232B2 (en) | 2006-01-19 | 2009-05-26 | Eli Lilly And Company | Process for the asymmetric synthesis of duloxetine |
| CA2640212A1 (en) * | 2006-02-13 | 2007-08-23 | Teva Pharmaceutical Industries Ltd. | A process for the preparation of (s)-(+)-n,n-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine, a duloxetine intermediate |
| HU228458B1 (en) * | 2006-03-13 | 2013-03-28 | Egis Gyogyszergyar Nyrt | Duloxetine salts for producing pharmaceutical compositions |
| SI1857451T1 (sl) | 2006-05-05 | 2010-11-30 | Fidia Farmaceutici | Postopek priprave intermediata ki je uporaben zaasimetrično sintezo duloksetina |
| US20080027128A1 (en) * | 2006-05-23 | 2008-01-31 | Santiago Ini | Duloxetine HCL polymorphs |
| EP2044049A2 (en) | 2006-07-03 | 2009-04-08 | Ranbaxy Laboratories Limited | Process for the preparation of enantiomerically pure salts of n-methyl- 3 -( 1-naph-thaleneoxy)- 3 - (-2-thienyl) propanamine |
| CZ300116B6 (cs) * | 2006-12-05 | 2009-02-11 | Zentiva, A. S. | Zpusob cištení hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu |
| HU227730B1 (en) | 2006-12-22 | 2012-01-30 | Richter Gedeon Nyrt | Process for the preparation of duloxetine and for their the intermediates |
| CN101657438A (zh) | 2006-12-22 | 2010-02-24 | 斯索恩有限公司 | 制备度洛西汀和相关化合物的方法 |
| US8269023B2 (en) | 2007-03-05 | 2012-09-18 | Lupin Ltd. | Process for preparation of duloxetine hydrochloride |
| WO2009019719A2 (en) * | 2007-08-09 | 2009-02-12 | Ind-Swift Laboratories Limited | Process for the preparation of 3-aryloxy-3-arylpropanamines |
| WO2009130708A2 (en) * | 2008-04-22 | 2009-10-29 | Shodhana Laboratories Limited | Preparation of duloxetine and its salts |
| WO2010025287A2 (en) | 2008-08-27 | 2010-03-04 | Codexis, Inc. | Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
| EP2329013B1 (en) | 2008-08-27 | 2015-10-28 | Codexis, Inc. | Ketoreductase polypeptides for the production of a 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
| WO2011033366A2 (en) | 2009-09-16 | 2011-03-24 | Jubilant Life Sciences Limited | Process for the preparation of duloxetine hydrochloride and its precursors |
| CN103360365A (zh) * | 2012-04-06 | 2013-10-23 | 李晓红 | 一种抗抑郁症药物原料药盐酸度洛西汀的制备新工艺 |
| CN104230882B (zh) * | 2014-08-29 | 2017-03-08 | 宁波美诺华药业股份有限公司 | 一种度洛西汀盐酸盐杂质的制备方法 |
| CN104829587B (zh) * | 2015-05-08 | 2017-07-21 | 上海万巷制药有限公司 | 盐酸度洛西汀的制备 |
| CN107382958B (zh) * | 2017-07-05 | 2021-11-09 | 浙江华海药业股份有限公司 | 一种度洛西汀中间体的结晶方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH578532A5 (https=) * | 1971-08-03 | 1976-08-13 | Cassella Farbwerke Mainkur Ag | |
| PL233786A1 (https=) | 1980-11-14 | 1982-05-24 | Lilly Co Eli | |
| US4777291A (en) * | 1985-02-27 | 1988-10-11 | Eli Lilly And Company | Racemization process |
| JPS62286959A (ja) * | 1986-06-05 | 1987-12-12 | Seitetsu Kagaku Co Ltd | 光学活性シアノカルニチン塩の製造方法 |
| US4956388A (en) * | 1986-12-22 | 1990-09-11 | Eli Lilly And Company | 3-aryloxy-3-substituted propanamines |
| KR880007433A (ko) * | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
| CA2042346A1 (en) * | 1990-05-17 | 1991-11-18 | Michael Alexander Staszak | Chiral synthesis of 1-aryl-3-aminopropan-1-ols |
| JPH09176157A (ja) * | 1992-12-09 | 1997-07-08 | Takeda Chem Ind Ltd | 光学活性アミノクマラン誘導体 |
| US5362886A (en) * | 1993-10-12 | 1994-11-08 | Eli Lilly And Company | Asymmetric synthesis |
| US6458955B1 (en) | 1994-12-16 | 2002-10-01 | Uop Llc | Process for preparation of pharmaceutically desired enantiomers |
| US6162949A (en) | 1994-12-16 | 2000-12-19 | Uop Llc | Process for preparation of the pharmaceutically desired (S)-oxetine enantiomers |
| EP0792649A1 (en) * | 1996-02-29 | 1997-09-03 | Eli Lilly And Company | Treatment of sleep disorders |
| HUP0101901A3 (en) * | 1998-05-22 | 2002-06-28 | Lilly Co Eli | Pharmaceutical composition for combined therapeutic treatment of refractory depression and combined treating process |
| CA2350531A1 (en) * | 1998-11-13 | 2000-05-25 | Smriti Iyengar | Method for treating pain |
| ATE309196T1 (de) * | 1999-04-09 | 2005-11-15 | Lilly Co Eli | Verfahren zur herstellung von 3-aryloxy-3- arylpropylamine und deren zwischenprodukte |
| WO2001044166A1 (en) * | 1999-12-17 | 2001-06-21 | Ranbaxy Laboratories Limited | Process for the preparation of fluoxetine hydrochloride |
| WO2003062219A1 (en) | 2002-01-24 | 2003-07-31 | Eli Lilly And Company | Process for preparing an intermediate useful for the asymmetric synthesis of duloxetine |
-
2002
- 2002-12-19 GB GBGB0229583.0A patent/GB0229583D0/en not_active Ceased
-
2003
- 2003-12-10 NZ NZ569874A patent/NZ569874A/en not_active IP Right Cessation
- 2003-12-10 CN CN2007101531328A patent/CN101125848B/zh not_active Expired - Fee Related
- 2003-12-10 JP JP2004561607A patent/JP5259048B2/ja not_active Expired - Fee Related
- 2003-12-10 RU RU2005122662/04A patent/RU2351594C2/ru not_active IP Right Cessation
- 2003-12-10 ES ES03767973T patent/ES2279971T3/es not_active Expired - Lifetime
- 2003-12-10 MX MXPA05006659A patent/MXPA05006659A/es active IP Right Grant
- 2003-12-10 HR HR20050657A patent/HRP20050657A2/hr not_active Application Discontinuation
- 2003-12-10 EP EP03767973A patent/EP1587801B1/en not_active Revoked
- 2003-12-10 AT AT03767973T patent/ATE353081T1/de not_active IP Right Cessation
- 2003-12-10 DE DE60311599T patent/DE60311599T2/de not_active Revoked
- 2003-12-10 AU AU2003292396A patent/AU2003292396B2/en not_active Ceased
- 2003-12-10 NZ NZ540881A patent/NZ540881A/en not_active IP Right Cessation
- 2003-12-10 EP EP06075798A patent/EP1690861B1/en not_active Expired - Lifetime
- 2003-12-10 KR KR1020057011506A patent/KR100926723B1/ko not_active Expired - Fee Related
- 2003-12-10 US US10/539,415 patent/US7645890B2/en not_active Expired - Fee Related
- 2003-12-10 PL PL377380A patent/PL377380A1/pl unknown
- 2003-12-10 PT PT03767973T patent/PT1587801E/pt unknown
- 2003-12-10 BR BR0316902-2A patent/BR0316902A/pt not_active IP Right Cessation
- 2003-12-10 CN CN200380109793A patent/CN100579975C/zh not_active Expired - Fee Related
- 2003-12-10 WO PCT/GB2003/005357 patent/WO2004056795A1/en not_active Ceased
- 2003-12-10 CA CA002510750A patent/CA2510750A1/en not_active Abandoned
-
2005
- 2005-06-16 IL IL169232A patent/IL169232A/en not_active IP Right Cessation
- 2005-06-17 TN TNP2005000167A patent/TNSN05167A1/en unknown
- 2005-06-24 IS IS7915A patent/IS7915A/is unknown
- 2005-07-14 ZA ZA200505656A patent/ZA200505656B/en unknown
- 2005-07-18 MA MA28400A patent/MA27706A1/fr unknown
-
2010
- 2010-01-14 AU AU2010200142A patent/AU2010200142B2/en not_active Ceased
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20141210 |