HRP20050657A2 - 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
- HRP20050657A2 HRP20050657A2 HR20050657A HRP20050657A HRP20050657A2 HR P20050657 A2 HRP20050657 A2 HR P20050657A2 HR 20050657 A HR20050657 A HR 20050657A HR P20050657 A HRP20050657 A HR P20050657A HR P20050657 A2 HRP20050657 A2 HR P20050657A2
- Authority
- HR
- Croatia
- Prior art keywords
- duloxetine
- addition salt
- acid
- acid addition
- formula
- Prior art date
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- 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 description 33
- 229960002866 duloxetine Drugs 0.000 title claims description 33
- 239000000543 intermediate Substances 0.000 title description 26
- 238000004519 manufacturing process Methods 0.000 title description 2
- 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 77
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 239000002253 acid Substances 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 63
- 230000008569 process Effects 0.000 claims abstract description 43
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- 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
- 238000006243 chemical reaction Methods 0.000 claims description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 16
- 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 12
- -1 (+) duloxetine di-p-toluyl tartrate Chemical class 0.000 claims description 10
- 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
- 239000003054 catalyst Substances 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 9
- 230000007704 transition Effects 0.000 claims description 9
- 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
- 230000017858 demethylation Effects 0.000 claims description 6
- 238000010520 demethylation reaction Methods 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 235000006408 oxalic acid Nutrition 0.000 claims description 5
- 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 4
- 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
- 239000012452 mother liquor Substances 0.000 claims description 3
- 150000003891 oxalate salts Chemical class 0.000 claims description 3
- 239000000825 pharmaceutical preparation 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
- 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
- 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
- 230000001335 demethylating effect Effects 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
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 claims description 2
- 229960002510 mandelic acid Drugs 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
- 229940095064 tartrate Drugs 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 239000003444 phase transfer catalyst Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 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
- 239000011541 reaction mixture Substances 0.000 description 10
- 230000006340 racemization Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000004090 dissolution Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 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
- 230000015572 biosynthetic process Effects 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
- CWLKTJOTWITYSI-UHFFFAOYSA-N 1-fluoronaphthalene Chemical compound C1=CC=C2C(F)=CC=CC2=C1 CWLKTJOTWITYSI-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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 class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 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
- 125000005534 decanoate group Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical class 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
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical class OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical class CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical class COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical class CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical class OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 150000001559 benzoic acids Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical class OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000005586 carbonic acid group Chemical group 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical class OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
- 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 150000002913 oxalic acids Chemical class 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000005498 phthalate group Chemical class 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 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-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid group Chemical group C(CCC(=O)O)(=O)O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (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 (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
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 |
---|---|
HRP20050657A2 true HRP20050657A2 (en) | 2005-10-31 |
Family
ID=9949985
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20050657A HRP20050657A2 (en) | 2002-12-19 | 2005-07-19 | A process for preparing duloxetine and intermediates for use therein |
Country Status (24)
Country | Link |
---|---|
US (1) | US7645890B2 (pt) |
EP (2) | EP1690861B1 (pt) |
JP (1) | JP5259048B2 (pt) |
KR (1) | KR100926723B1 (pt) |
CN (2) | CN100579975C (pt) |
AT (1) | ATE353081T1 (pt) |
AU (2) | AU2003292396B2 (pt) |
BR (1) | BR0316902A (pt) |
CA (1) | CA2510750A1 (pt) |
DE (1) | DE60311599T2 (pt) |
ES (1) | ES2279971T3 (pt) |
GB (1) | GB0229583D0 (pt) |
HR (1) | HRP20050657A2 (pt) |
IL (1) | IL169232A (pt) |
IS (1) | IS7915A (pt) |
MA (1) | MA27706A1 (pt) |
MX (1) | MXPA05006659A (pt) |
NZ (2) | NZ540881A (pt) |
PL (1) | PL377380A1 (pt) |
PT (1) | PT1587801E (pt) |
RU (1) | RU2351594C2 (pt) |
TN (1) | TNSN05167A1 (pt) |
WO (1) | WO2004056795A1 (pt) |
ZA (1) | ZA200505656B (pt) |
Families Citing this family (32)
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WO2006027798A2 (en) * | 2004-08-05 | 2006-03-16 | Sun Pharmaceutical Industries Limited | A process for preparation of an antidepressant 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) |
JP2007523213A (ja) * | 2004-12-23 | 2007-08-16 | テバ ファーマシューティカル インダストリーズ リミティド | 医薬的に許容できるデュロキセチンの塩及びその中間体の調製方法 |
WO2006081515A2 (en) * | 2005-01-27 | 2006-08-03 | Teva Pharmaceutical Industries Ltd. | Duloxetine hydrochloride polymorphs |
MX2007010931A (es) * | 2005-03-08 | 2007-10-16 | Teva Pharma | Formas cristalinas de (s)-(+)-n,n-dimetil-3-(1-naftaleniloxi)-3-(2 -tienil)propanamina oxalato y la preparacion ellas. |
EP1874754A1 (en) * | 2005-03-14 | 2008-01-09 | Teva Pharmaceutical Industries Ltd | 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 |
US7842717B2 (en) | 2005-09-22 | 2010-11-30 | Teva Pharmaceutical Industries Ltd. | DNT-maleate and methods of preparation thereof |
US7759500B2 (en) | 2005-12-05 | 2010-07-20 | Teva Pharmaceutical Industries Ltd. | 2-(N-methyl-propanamine)-3-(2-naphthol)thiophene, an impurity of duloxetine hydrochloride |
CA2634007A1 (en) * | 2005-12-12 | 2007-08-30 | 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 |
WO2007077580A2 (en) * | 2006-01-06 | 2007-07-12 | Msn Laboratories Limited | Improved process for pure duloxetine hydrochloride |
US7538232B2 (en) | 2006-01-19 | 2009-05-26 | Eli Lilly And Company | Process for the asymmetric synthesis of duloxetine |
EP1976845A2 (en) * | 2006-02-13 | 2008-10-08 | 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 |
PT1857451E (pt) | 2006-05-05 | 2010-10-25 | Fidia Farmaceutici | Processo para a preparação de uma substância intermédia útil para a síntese assimétrica da (+)duloxetina |
CN101448815A (zh) * | 2006-05-23 | 2009-06-03 | 特瓦制药工业有限公司 | 度洛西汀hci多晶型物 |
CN101484435A (zh) | 2006-07-03 | 2009-07-15 | 兰贝克赛实验室有限公司 | 制备n-甲基-3-(1-萘氧基)-3-(2-噻吩基)丙胺及其纯对应异构体盐的方法 |
CZ300116B6 (cs) * | 2006-12-05 | 2009-02-11 | Zentiva, A. S. | Zpusob cištení hydrochloridu (S)-N-methyl-3-(1-naftyloxy)-3-(2-thienyl)propylaminu |
EP2114912B1 (en) | 2006-12-22 | 2012-04-04 | Synthon B.V. | Process for making duloxetine and related compounds |
HU227730B1 (en) | 2006-12-22 | 2012-01-30 | Richter Gedeon Nyrt | Process for the preparation of duloxetine and for their the intermediates |
EP2132192B1 (en) | 2007-03-05 | 2013-04-24 | Lupin Limited | Novel 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 |
WO2010025238A2 (en) | 2008-08-27 | 2010-03-04 | Codexis, Inc. | Ketoreductase polypeptides for the production of a 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
US8288141B2 (en) | 2008-08-27 | 2012-10-16 | Codexis, Inc. | Ketoreductase polypeptides for the production of 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 (15)
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CH578532A5 (pt) * | 1971-08-03 | 1976-08-13 | Cassella Farbwerke Mainkur Ag | |
PL233786A1 (pt) | 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 |
KR880007433A (ko) * | 1986-12-22 | 1988-08-27 | 메리 앤 터커 | 3-아릴옥시-3-치환된 프로판아민 |
US4956388A (en) * | 1986-12-22 | 1990-09-11 | Eli Lilly And Company | 3-aryloxy-3-substituted propanamines |
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 |
US6162949A (en) | 1994-12-16 | 2000-12-19 | Uop Llc | Process for preparation of the pharmaceutically desired (S)-oxetine enantiomers |
US6458955B1 (en) | 1994-12-16 | 2002-10-01 | Uop Llc | Process for preparation of pharmaceutically desired enantiomers |
JP2002529499A (ja) | 1998-11-13 | 2002-09-10 | イーライ・リリー・アンド・カンパニー | 痛みの治療方法 |
WO2000061540A1 (en) * | 1999-04-09 | 2000-10-19 | Eli Lilly And Company | Methods for preparing 3-aryloxy-3-arylpropylamines and intermediates thereof |
US6677485B2 (en) * | 1999-12-17 | 2004-01-13 | 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 MX MXPA05006659A patent/MXPA05006659A/es active IP Right Grant
- 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 KR KR1020057011506A patent/KR100926723B1/ko not_active IP Right Cessation
- 2003-12-10 AU AU2003292396A patent/AU2003292396B2/en not_active Ceased
- 2003-12-10 CA CA002510750A patent/CA2510750A1/en not_active Abandoned
- 2003-12-10 JP JP2004561607A patent/JP5259048B2/ja not_active Expired - Fee Related
- 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 EP EP06075798A patent/EP1690861B1/en not_active Expired - Lifetime
- 2003-12-10 ES ES03767973T patent/ES2279971T3/es not_active Expired - Lifetime
- 2003-12-10 WO PCT/GB2003/005357 patent/WO2004056795A1/en active IP Right Grant
- 2003-12-10 CN CN200380109793A patent/CN100579975C/zh not_active Expired - Fee Related
- 2003-12-10 AT AT03767973T patent/ATE353081T1/de not_active IP Right Cessation
- 2003-12-10 NZ NZ540881A patent/NZ540881A/en not_active IP Right Cessation
- 2003-12-10 NZ NZ569874A patent/NZ569874A/en not_active IP Right Cessation
- 2003-12-10 RU RU2005122662/04A patent/RU2351594C2/ru not_active IP Right Cessation
- 2003-12-10 CN CN2007101531328A patent/CN101125848B/zh not_active Expired - Fee Related
- 2003-12-10 DE DE60311599T patent/DE60311599T2/de not_active Revoked
- 2003-12-10 EP EP03767973A patent/EP1587801B1/en not_active Revoked
-
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
- 2005-07-19 HR HR20050657A patent/HRP20050657A2/hr not_active Application Discontinuation
-
2010
- 2010-01-14 AU AU2010200142A patent/AU2010200142B2/en not_active Ceased
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