ES2377862T3 - Procedimiento para la fabricación de [fenilsulfanilfenil]piperidinas - Google Patents
Procedimiento para la fabricación de [fenilsulfanilfenil]piperidinas Download PDFInfo
- Publication number
- ES2377862T3 ES2377862T3 ES09717792T ES09717792T ES2377862T3 ES 2377862 T3 ES2377862 T3 ES 2377862T3 ES 09717792 T ES09717792 T ES 09717792T ES 09717792 T ES09717792 T ES 09717792T ES 2377862 T3 ES2377862 T3 ES 2377862T3
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- Prior art keywords
- compound
- alkyl
- formula
- process according
- acid
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 34
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- NUVVEDILYSTVDX-UHFFFAOYSA-N 1-(2-phenylsulfanylphenyl)piperidine Chemical class C1CCCCN1C1=CC=CC=C1SC1=CC=CC=C1 NUVVEDILYSTVDX-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical class C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 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 abstract description 6
- 150000003839 salts Chemical class 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- -1 alkyl magnesium Chemical compound 0.000 claims description 23
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 19
- 150000007513 acids Chemical class 0.000 claims description 15
- LPLUHSYAFSMXGF-UHFFFAOYSA-N 1-benzyl-4-[2-(4-methylphenyl)sulfanylphenyl]piperidin-4-ol Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1C1(O)CCN(CC=2C=CC=CC=2)CC1 LPLUHSYAFSMXGF-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 8
- 239000011777 magnesium Substances 0.000 claims description 8
- 229910052749 magnesium Inorganic materials 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- 238000006263 metalation reaction Methods 0.000 claims description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 claims description 3
- WCZWFNWHXKDCFB-UHFFFAOYSA-N ethyl 4-ethoxycarbonyloxy-4-[2-(4-methylphenyl)sulfanylphenyl]piperidine-1-carboxylate Chemical compound C=1C=CC=C(SC=2C=CC(C)=CC=2)C=1C1(OC(=O)OCC)CCN(C(=O)OCC)CC1 WCZWFNWHXKDCFB-UHFFFAOYSA-N 0.000 claims description 3
- 239000003446 ligand Substances 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 238000001465 metallisation Methods 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 239000002904 solvent Substances 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 20
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012071 phase Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000005292 vacuum distillation Methods 0.000 description 8
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 7
- CVASBKDYSQKLSO-UHFFFAOYSA-N Tedatioxetine Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1C1CCNCC1 CVASBKDYSQKLSO-UHFFFAOYSA-N 0.000 description 6
- 238000005191 phase separation Methods 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- CYUPFFKTTJMWLE-UHFFFAOYSA-N 1-bromo-2-(4-methylphenyl)sulfanylbenzene Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1Br CYUPFFKTTJMWLE-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 235000017550 sodium carbonate Nutrition 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 239000012296 anti-solvent Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000000634 powder X-ray diffraction Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 229960004592 isopropanol Drugs 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- CPZFPNKPHBCUOB-UHFFFAOYSA-N 1-methyl-4-phenylsulfanylbenzene Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1 CPZFPNKPHBCUOB-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- WQONPSCCEXUXTQ-UHFFFAOYSA-N 1,2-dibromobenzene Chemical compound BrC1=CC=CC=C1Br WQONPSCCEXUXTQ-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- UPFGXZXCORMNNT-UHFFFAOYSA-N 1-(3-methyl-2-phenylsulfanylphenyl)piperidine Chemical class C=1C=CC=CC=1SC=1C(C)=CC=CC=1N1CCCCC1 UPFGXZXCORMNNT-UHFFFAOYSA-N 0.000 description 1
- NZAXGZYPZGEVBD-UHFFFAOYSA-N 1-benzoylpiperidin-4-one Chemical compound C=1C=CC=CC=1C(=O)N1CCC(=O)CC1 NZAXGZYPZGEVBD-UHFFFAOYSA-N 0.000 description 1
- KLWBXZBDHNRVLZ-UHFFFAOYSA-N 1-phenylmethoxypiperidin-4-one Chemical compound C1CC(=O)CCN1OCC1=CC=CC=C1 KLWBXZBDHNRVLZ-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-M 4-bromobenzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-M 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- WRWCBEDBMQKWAP-UHFFFAOYSA-N [4-hydroxy-4-[2-(4-methylphenyl)sulfanylphenyl]piperidin-1-yl]-phenylmethanone Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1C1(O)CCN(C(=O)C=2C=CC=CC=2)CC1 WRWCBEDBMQKWAP-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical class C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- CMVAYPJYRXHDOB-UHFFFAOYSA-N ethyl 2-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1=O CMVAYPJYRXHDOB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- JOXNAPLQMZNQGR-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-[2-(4-methylphenyl)sulfanylphenyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1C1(O)CCN(C(=O)OC(C)(C)C)CC1 JOXNAPLQMZNQGR-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3309308P | 2008-03-03 | 2008-03-03 | |
| DKPA200800314 | 2008-03-03 | ||
| DK200800314 | 2008-03-03 | ||
| US33093P | 2008-03-03 | ||
| PCT/EP2009/052440 WO2009109541A1 (en) | 2008-03-03 | 2009-03-02 | Process for the manufacture of [phenylsulfanylphenyl]piperidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2377862T3 true ES2377862T3 (es) | 2012-04-02 |
Family
ID=40547924
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09717792T Active ES2377862T3 (es) | 2008-03-03 | 2009-03-02 | Procedimiento para la fabricación de [fenilsulfanilfenil]piperidinas |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US8362255B2 (OSRAM) |
| EP (1) | EP2260024B1 (OSRAM) |
| JP (1) | JP5564439B2 (OSRAM) |
| KR (1) | KR20100122914A (OSRAM) |
| CN (1) | CN101959859B (OSRAM) |
| AR (1) | AR070737A1 (OSRAM) |
| AT (1) | ATE539055T1 (OSRAM) |
| AU (1) | AU2009221170B2 (OSRAM) |
| BR (1) | BRPI0908166A2 (OSRAM) |
| CA (1) | CA2715579A1 (OSRAM) |
| CL (1) | CL2009000490A1 (OSRAM) |
| CO (1) | CO6290758A2 (OSRAM) |
| CY (1) | CY1113887T1 (OSRAM) |
| DK (1) | DK2260024T3 (OSRAM) |
| EA (1) | EA017855B1 (OSRAM) |
| ES (1) | ES2377862T3 (OSRAM) |
| HR (1) | HRP20120118T1 (OSRAM) |
| IL (1) | IL207471A (OSRAM) |
| MX (1) | MX2010008729A (OSRAM) |
| NZ (1) | NZ587593A (OSRAM) |
| PL (1) | PL2260024T3 (OSRAM) |
| PT (1) | PT2260024E (OSRAM) |
| RS (1) | RS52128B (OSRAM) |
| SI (1) | SI2260024T1 (OSRAM) |
| TW (1) | TW200940505A (OSRAM) |
| UA (1) | UA98698C2 (OSRAM) |
| WO (1) | WO2009109541A1 (OSRAM) |
| ZA (1) | ZA201006135B (OSRAM) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8299095B2 (en) * | 2006-06-16 | 2012-10-30 | H. Lundbeck A/S | Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl] piperidine with combined serotonin and norepinephrine reuptake inhibition and uses thereof |
| JP2012163850A (ja) * | 2011-02-08 | 2012-08-30 | Nippon Sheet Glass Co Ltd | 正立等倍レンズアレイプレート、光走査ユニット、画像読取装置および画像書込装置 |
| US8987457B2 (en) | 2012-05-21 | 2015-03-24 | Novartis Ag | Ring-substituted N-pyridinyl amides as kinase inhibitors |
| CN104710345B (zh) * | 2013-12-17 | 2017-09-05 | 江苏恩华药业股份有限公司 | 用于制备4‑（2‑（4‑甲基苯基硫基））苯基哌啶的化合物、其制备方法及应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2324087A (en) * | 1997-04-10 | 1998-10-14 | Merck & Co Inc | Preparation of (S)-3-Carbethoxy-3-benzylpiperidine |
| WO2001046147A1 (en) | 1999-12-20 | 2001-06-28 | Eli Lilly And Company | A process for preparing 4-substituted piperidines |
| UA81749C2 (uk) * | 2001-10-04 | 2008-02-11 | Х. Луннбек А/С | Фенілпіперазинові похідні як інгібітори зворотного захоплення серотоніну |
| UA81300C2 (en) * | 2003-04-04 | 2007-12-25 | Lundbeck & Co As H | Derivates of 4-(2-fenilsulfanilfenil)-1,2,3,6-tetrahydropiridin as retarding agents of serotonin recapture |
| DK1626720T3 (da) * | 2003-04-04 | 2008-12-01 | Lundbeck & Co As H | 4-(2-Phenylsulfanyl-phenyl)-piperidinderivater som serotonin-genoptagelseshæmmer |
| US8299095B2 (en) * | 2006-06-16 | 2012-10-30 | H. Lundbeck A/S | Crystalline forms of 4-[2-(4-methylphenylsulfanyl)-phenyl] piperidine with combined serotonin and norepinephrine reuptake inhibition and uses thereof |
-
2009
- 2009-02-03 UA UAA201011031A patent/UA98698C2/ru unknown
- 2009-02-19 TW TW098105235A patent/TW200940505A/zh unknown
- 2009-03-02 AT AT09717792T patent/ATE539055T1/de active
- 2009-03-02 RS RS20120063A patent/RS52128B/sr unknown
- 2009-03-02 JP JP2010549114A patent/JP5564439B2/ja not_active Expired - Fee Related
- 2009-03-02 NZ NZ587593A patent/NZ587593A/en not_active IP Right Cessation
- 2009-03-02 DK DK09717792.7T patent/DK2260024T3/da active
- 2009-03-02 ES ES09717792T patent/ES2377862T3/es active Active
- 2009-03-02 EA EA201071025A patent/EA017855B1/ru not_active IP Right Cessation
- 2009-03-02 MX MX2010008729A patent/MX2010008729A/es active IP Right Grant
- 2009-03-02 HR HR20120118T patent/HRP20120118T1/hr unknown
- 2009-03-02 AR ARP090100734A patent/AR070737A1/es unknown
- 2009-03-02 PT PT09717792T patent/PT2260024E/pt unknown
- 2009-03-02 SI SI200930184T patent/SI2260024T1/sl unknown
- 2009-03-02 BR BRPI0908166-6A patent/BRPI0908166A2/pt not_active IP Right Cessation
- 2009-03-02 EP EP09717792A patent/EP2260024B1/en active Active
- 2009-03-02 US US12/920,357 patent/US8362255B2/en not_active Expired - Fee Related
- 2009-03-02 CN CN200980108235XA patent/CN101959859B/zh not_active Expired - Fee Related
- 2009-03-02 WO PCT/EP2009/052440 patent/WO2009109541A1/en not_active Ceased
- 2009-03-02 CL CL2009000490A patent/CL2009000490A1/es unknown
- 2009-03-02 PL PL09717792T patent/PL2260024T3/pl unknown
- 2009-03-02 CA CA2715579A patent/CA2715579A1/en not_active Abandoned
- 2009-03-02 KR KR1020107019480A patent/KR20100122914A/ko not_active Ceased
- 2009-03-02 AU AU2009221170A patent/AU2009221170B2/en not_active Ceased
-
2010
- 2010-08-08 IL IL207471A patent/IL207471A/en not_active IP Right Cessation
- 2010-08-27 ZA ZA2010/06135A patent/ZA201006135B/en unknown
- 2010-09-02 CO CO10108740A patent/CO6290758A2/es active IP Right Grant
-
2012
- 2012-02-13 CY CY20121100145T patent/CY1113887T1/el unknown
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