CS207748B2 - Method of making the derivatives of the hexahydroazepine,piperidine or pyrrolidine - Google Patents
Method of making the derivatives of the hexahydroazepine,piperidine or pyrrolidine Download PDFInfo
- Publication number
- CS207748B2 CS207748B2 CS788756A CS875678A CS207748B2 CS 207748 B2 CS207748 B2 CS 207748B2 CS 788756 A CS788756 A CS 788756A CS 875678 A CS875678 A CS 875678A CS 207748 B2 CS207748 B2 CS 207748B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- carbon atoms
- formula
- compound
- alkyl
- hydrogen
- Prior art date
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims description 18
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 57
- 125000003118 aryl group Chemical group 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- -1 3,3-disubstituted-hexahydroazepine Chemical class 0.000 claims abstract description 31
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 22
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N Caprolactam Natural products O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 claims abstract description 9
- XUWHAWMETYGRKB-UHFFFAOYSA-N delta-valerolactam Natural products O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims abstract description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Natural products O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 96
- 125000004432 carbon atom Chemical group C* 0.000 claims description 77
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 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 17
- 150000003235 pyrrolidines Chemical class 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 239000007858 starting material Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 7
- 238000007126 N-alkylation reaction Methods 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000005661 deetherification reaction Methods 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 230000000202 analgesic effect Effects 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000000203 mixture Substances 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 229940043279 diisopropylamine Drugs 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 239000010410 layer Substances 0.000 description 11
- 239000008346 aqueous phase Substances 0.000 description 10
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 10
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 150000003951 lactams Chemical class 0.000 description 9
- 238000001816 cooling Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- XJZQHHIPUDRJGJ-UHFFFAOYSA-N 1-methyl-3-(3-oxocyclohexen-1-yl)azepan-2-one Chemical compound O=C1N(C)CCCCC1C1=CC(=O)CCC1 XJZQHHIPUDRJGJ-UHFFFAOYSA-N 0.000 description 4
- IBNKFKLIUOMAQB-UHFFFAOYSA-N 3-(3-hydroxyphenyl)-1-methylazepan-2-one Chemical compound O=C1N(C)CCCCC1C1=CC=CC(O)=C1 IBNKFKLIUOMAQB-UHFFFAOYSA-N 0.000 description 4
- IMCGYHPRALKTOL-UHFFFAOYSA-N 3-(3-hydroxyphenyl)azepan-2-one Chemical compound OC1=CC=CC(C2C(NCCCC2)=O)=C1 IMCGYHPRALKTOL-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 150000003053 piperidines Chemical class 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- HZASYDHQJZKOCU-UHFFFAOYSA-N 3-(3-oxocyclohexen-1-yl)azepan-2-one Chemical compound O=C1CCCC(C2C(NCCCC2)=O)=C1 HZASYDHQJZKOCU-UHFFFAOYSA-N 0.000 description 3
- YFSJZMANJNLCOQ-UHFFFAOYSA-N 3-ethyl-3-(3-hydroxyphenyl)-1-methylazepan-2-one Chemical compound C=1C=CC(O)=CC=1C1(CC)CCCCN(C)C1=O YFSJZMANJNLCOQ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical compound CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 3
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 150000003335 secondary amines Chemical group 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- GGYVTHJIUNGKFZ-UHFFFAOYSA-N 1-methylpiperidin-2-one Chemical compound CN1CCCCC1=O GGYVTHJIUNGKFZ-UHFFFAOYSA-N 0.000 description 2
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 2
- XMSWGYQEWPUOKA-UHFFFAOYSA-N 2-[3-(3-hydroxyphenyl)-2,3-dimethylpiperidin-1-yl]-1-phenylethanone Chemical compound C1CCC(C=2C=C(O)C=CC=2)(C)C(C)N1CC(=O)C1=CC=CC=C1 XMSWGYQEWPUOKA-UHFFFAOYSA-N 0.000 description 2
- VFUGCQKESINERB-UHFFFAOYSA-N 3-(1-methyl-3-propylpyrrolidin-3-yl)phenol Chemical compound C=1C=CC(O)=CC=1C1(CCC)CCN(C)C1 VFUGCQKESINERB-UHFFFAOYSA-N 0.000 description 2
- JLICHNCFTLFZJN-UHFFFAOYSA-N 3-(3-ethyl-1-methyl-3-azepanyl)phenol Chemical compound C=1C=CC(O)=CC=1C1(CC)CCCCN(C)C1 JLICHNCFTLFZJN-UHFFFAOYSA-N 0.000 description 2
- NNRAHZOEQXAXAF-UHFFFAOYSA-N 3-(3-hydroxyphenyl)-1-methyl-3-propylpyrrolidin-2-one Chemical compound C=1C=CC(O)=CC=1C1(CCC)CCN(C)C1=O NNRAHZOEQXAXAF-UHFFFAOYSA-N 0.000 description 2
- UJLKWEKIONGLJO-UHFFFAOYSA-N 3-(3-hydroxyphenyl)-1-methylpyrrolidin-2-one Chemical compound O=C1N(C)CCC1C1=CC=CC(O)=C1 UJLKWEKIONGLJO-UHFFFAOYSA-N 0.000 description 2
- HPYQDDXKEGCTGC-UHFFFAOYSA-N 3-(3-methoxyphenyl)-1-methylazepan-2-one Chemical compound COC1=CC=CC(C2C(N(C)CCCC2)=O)=C1 HPYQDDXKEGCTGC-UHFFFAOYSA-N 0.000 description 2
- PHWHMJKWJICNLX-UHFFFAOYSA-N 3-ethyl-1-methyl-3-(3-oxocyclohexen-1-yl)azepan-2-one Chemical compound C=1C(=O)CCCC=1C1(CC)CCCCN(C)C1=O PHWHMJKWJICNLX-UHFFFAOYSA-N 0.000 description 2
- AFBQUXAODCBPRJ-UHFFFAOYSA-N 3-ethyl-3-(3-methoxyphenyl)-1-methylazepan-2-one Chemical compound C=1C=CC(OC)=CC=1C1(CC)CCCCN(C)C1=O AFBQUXAODCBPRJ-UHFFFAOYSA-N 0.000 description 2
- JFTPIEHHCQPVCS-UHFFFAOYSA-N 3-methoxycyclohex-2-en-1-one Chemical compound COC1=CC(=O)CCC1 JFTPIEHHCQPVCS-UHFFFAOYSA-N 0.000 description 2
- IISFUJKHMFGYOU-UHFFFAOYSA-N 3-propan-2-yloxycyclohex-2-en-1-one Chemical compound CC(C)OC1=CC(=O)CCC1 IISFUJKHMFGYOU-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002585 base 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
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 125000000596 cyclohexenyl group Chemical class C1(=CCCCC1)* 0.000 description 2
- 239000002027 dichloromethane extract Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000003918 fraction a Anatomy 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 2
- JLICHNCFTLFZJN-HNNXBMFYSA-N meptazinol Chemical compound C=1C=CC(O)=CC=1[C@@]1(CC)CCCCN(C)C1 JLICHNCFTLFZJN-HNNXBMFYSA-N 0.000 description 2
- 229960000365 meptazinol Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229950009273 myfadol Drugs 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229950004859 profadol Drugs 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- XVENYIRISFAOOJ-UHFFFAOYSA-N 1-benzyl-3-(3-hydroxyphenyl)azepan-2-one Chemical compound OC1=CC=CC(C2C(N(CC=3C=CC=CC=3)CCCC2)=O)=C1 XVENYIRISFAOOJ-UHFFFAOYSA-N 0.000 description 1
- DJGIITKNTHQYPX-UHFFFAOYSA-N 1-benzylazepan-2-one Chemical compound O=C1CCCCCN1CC1=CC=CC=C1 DJGIITKNTHQYPX-UHFFFAOYSA-N 0.000 description 1
- HZFQGYWRFABYSR-UHFFFAOYSA-N 1-methoxycyclohexene Chemical compound COC1=CCCCC1 HZFQGYWRFABYSR-UHFFFAOYSA-N 0.000 description 1
- YEVCQAHYSHCAQO-UHFFFAOYSA-N 1-methyl-3-(3-oxocyclohexen-1-yl)piperidin-2-one Chemical compound O=C1N(C)CCCC1C1=CC(=O)CCC1 YEVCQAHYSHCAQO-UHFFFAOYSA-N 0.000 description 1
- DCALJVULAGICIX-UHFFFAOYSA-N 1-propylpyrrolidin-2-one Chemical compound CCCN1CCCC1=O DCALJVULAGICIX-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- JYJURPHZXCLFDX-UHFFFAOYSA-N 2-methoxycyclohexan-1-one Chemical compound COC1CCCCC1=O JYJURPHZXCLFDX-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BOQRNIWPRAIAAL-UHFFFAOYSA-N 2-propan-2-yloxycyclohexan-1-one Chemical compound CC(C)OC1CCCCC1=O BOQRNIWPRAIAAL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- LBJMODGXTMCLCY-UHFFFAOYSA-N 3-(1,3-dimethylazepan-3-yl)phenol Chemical compound OC=1C=C(C=CC1)C1(CN(CCCC1)C)C LBJMODGXTMCLCY-UHFFFAOYSA-N 0.000 description 1
- VGQKVJSOSDFCAT-UHFFFAOYSA-N 3-(3-ethyl-1-prop-2-ynylazepan-3-yl)phenol Chemical compound C=1C=CC(O)=CC=1C1(CC)CCCCN(CC#C)C1 VGQKVJSOSDFCAT-UHFFFAOYSA-N 0.000 description 1
- NCFRCSCRTCXVHY-UHFFFAOYSA-N 3-(3-ethyl-1-propylazepan-3-yl)phenol Chemical compound C(C)C1(CN(CCCC1)CCC)C1=CC(=CC=C1)O NCFRCSCRTCXVHY-UHFFFAOYSA-N 0.000 description 1
- HNPRIQQMQGLGID-UHFFFAOYSA-N 3-(3-hydroxyphenyl)-1-methylpiperidin-2-one Chemical compound O=C1N(C)CCCC1C1=CC=CC(O)=C1 HNPRIQQMQGLGID-UHFFFAOYSA-N 0.000 description 1
- LDNFLWJRDDURLP-UHFFFAOYSA-N 3-(3-methoxyphenyl)azepan-2-one Chemical compound COC1=CC=CC(C2C(NCCCC2)=O)=C1 LDNFLWJRDDURLP-UHFFFAOYSA-N 0.000 description 1
- TWJOWUPSYFIBKC-UHFFFAOYSA-N 3-(3-methoxyphenyl)azepane Chemical compound COC1=CC=CC(C2CNCCCC2)=C1 TWJOWUPSYFIBKC-UHFFFAOYSA-N 0.000 description 1
- LINAMJDHAYLHGQ-UHFFFAOYSA-N 3-(3-phenylmethoxyphenyl)azepan-2-one Chemical compound O=C1NCCCCC1C1=CC=CC(OCC=2C=CC=CC=2)=C1 LINAMJDHAYLHGQ-UHFFFAOYSA-N 0.000 description 1
- LCMJIARZHZRCNZ-UHFFFAOYSA-N 3-(3-propylazepan-3-yl)phenol Chemical compound OC=1C=C(C=CC1)C1(CNCCCC1)CCC LCMJIARZHZRCNZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- WDGUISOEXDGLTB-UHFFFAOYSA-N 3-butyl-3-(3-hydroxyphenyl)-1-methylazepan-2-one Chemical compound C=1C=CC(O)=CC=1C1(CCCC)CCCCN(C)C1=O WDGUISOEXDGLTB-UHFFFAOYSA-N 0.000 description 1
- TWJZVJYUCAHEGB-UHFFFAOYSA-N 3-ethyl-1-methylazepan-2-one Chemical compound CCC1CCCCN(C)C1=O TWJZVJYUCAHEGB-UHFFFAOYSA-N 0.000 description 1
- FBHTUAAEMVHAJT-UHFFFAOYSA-N 3-ethyl-3-(2-methoxyphenyl)azepan-2-one Chemical compound C=1C=CC=C(OC)C=1C1(CC)CCCCNC1=O FBHTUAAEMVHAJT-UHFFFAOYSA-N 0.000 description 1
- MJHKYIKIHNDTBK-UHFFFAOYSA-N 3-ethyl-3-(3-methoxyphenyl)-1-methylazepane Chemical compound C=1C=CC(OC)=CC=1C1(CC)CCCCN(C)C1 MJHKYIKIHNDTBK-UHFFFAOYSA-N 0.000 description 1
- QHRHMXLAEBLVPG-UHFFFAOYSA-N 3-ethyl-3-(3-methoxyphenyl)azepan-2-one Chemical compound C=1C=CC(OC)=CC=1C1(CC)CCCCNC1=O QHRHMXLAEBLVPG-UHFFFAOYSA-N 0.000 description 1
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine 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
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- PBGGNZZGJIKBMJ-UHFFFAOYSA-N di(propan-2-yl)azanide Chemical compound CC(C)[N-]C(C)C PBGGNZZGJIKBMJ-UHFFFAOYSA-N 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- GMTCPFCMAHMEMT-UHFFFAOYSA-N n-decyldecan-1-amine Chemical compound CCCCCCCCCCNCCCCCCCCCC GMTCPFCMAHMEMT-UHFFFAOYSA-N 0.000 description 1
- UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 description 1
- KZOPSPQZLMCNPF-UHFFFAOYSA-N n-tert-butyl-2-methylbutan-2-amine Chemical compound CCC(C)(C)NC(C)(C)C KZOPSPQZLMCNPF-UHFFFAOYSA-N 0.000 description 1
- CATWEXRJGNBIJD-UHFFFAOYSA-N n-tert-butyl-2-methylpropan-2-amine Chemical compound CC(C)(C)NC(C)(C)C CATWEXRJGNBIJD-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000012260 resinous material Substances 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- 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
- C07D211/20—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 singly bound oxygen or sulphur atoms
- C07D211/22—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 singly bound oxygen or sulphur atoms by oxygen atoms
-
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/04—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/08—Oxygen atoms
- C07D223/10—Oxygen atoms attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB53370/77A GB1593888A (en) | 1977-12-22 | 1977-12-22 | Hexahydroazepine piperidine and pyrrolidine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS207748B2 true CS207748B2 (en) | 1981-08-31 |
Family
ID=10467561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS788756A CS207748B2 (en) | 1977-12-22 | 1978-12-21 | Method of making the derivatives of the hexahydroazepine,piperidine or pyrrolidine |
Country Status (33)
| Country | Link |
|---|---|
| US (2) | US4197239A (it) |
| EP (1) | EP0003253B1 (it) |
| JP (1) | JPS5488286A (it) |
| AR (1) | AR221710A1 (it) |
| AT (1) | AT373586B (it) |
| AU (1) | AU519653B2 (it) |
| CA (2) | CA1113092A (it) |
| CS (1) | CS207748B2 (it) |
| CY (2) | CY1144A (it) |
| DD (2) | DD141308A5 (it) |
| DE (1) | DE2862139D1 (it) |
| DK (1) | DK156302C (it) |
| EG (1) | EG13745A (it) |
| ES (2) | ES476160A1 (it) |
| FI (1) | FI70575C (it) |
| GB (1) | GB1593888A (it) |
| GR (1) | GR64029B (it) |
| HK (2) | HK18082A (it) |
| HU (1) | HU181997B (it) |
| IE (1) | IE47631B1 (it) |
| IL (1) | IL55924A (it) |
| IN (1) | IN150193B (it) |
| IT (1) | IT1102761B (it) |
| KE (2) | KE3206A (it) |
| MX (1) | MX5628E (it) |
| MY (2) | MY8200279A (it) |
| NZ (1) | NZ188863A (it) |
| PH (2) | PH14412A (it) |
| PL (1) | PL126008B1 (it) |
| PT (1) | PT68962A (it) |
| SU (1) | SU1301311A3 (it) |
| YU (1) | YU40543B (it) |
| ZA (1) | ZA786244B (it) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE11046T1 (de) * | 1979-07-03 | 1985-01-15 | John Wyeth & Brother Limited | Verfahren zur herstellung von 2-oxo- und 2unsubstituierten hexahydroazepinderivaten. |
| IE54154B1 (en) * | 1981-12-02 | 1989-07-05 | Wyeth John & Brother Ltd | M-hydroxyphenyl substituted compounds |
| US5665754A (en) * | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| SE0001438D0 (sv) | 2000-04-18 | 2000-04-18 | Axon Chemicals Bv | New chemical compounds and their use in therapy |
| KR100421282B1 (ko) * | 2001-08-22 | 2004-03-09 | 부광약품 주식회사 | 1-메틸헥사히드로-4-아제피논 염산염의 제조방법 |
| CN101035765B (zh) * | 2004-07-13 | 2010-10-13 | 弗·哈夫曼-拉罗切有限公司 | 磺酰胺衍生物 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2524643A (en) * | 1947-12-04 | 1950-10-03 | Maltbie Lab Inc | 3-phenyl-2-piperidones |
| US3149123A (en) * | 1961-01-04 | 1964-09-15 | Parke Davis & Co | 1, 3-dialkyl-3-oxyphenylpyrrolidine compounds |
| NL265485A (it) * | 1961-06-02 | |||
| FR1337793A (fr) * | 1962-06-19 | 1963-09-20 | Parke Davis & Co | Composés de pyrrolidine et procédé de préparation de ces composés |
| GB1285025A (en) * | 1968-08-16 | 1972-08-09 | Wyeth John & Brother Ltd | Hexahydroazepines |
| CH526536A (de) * | 1970-02-05 | 1972-08-15 | Sandoz Ag | Verfahren zur Herstellung neuer 3-Phenylpyrrolidinderivate |
| CH526534A (de) * | 1970-02-05 | 1972-08-15 | Sandoz Ag | Verfahren zur Herstellung neuer Pyrrolidin-1-carboxamidinderivate |
| CH526535A (de) * | 1970-02-05 | 1972-08-15 | Sandoz Ag | Verfahren zur Herstellung neuer Pyrrolidin-1-carboxamidinderivate |
| US3729465A (en) * | 1971-02-03 | 1973-04-24 | Wyeth John & Brother Ltd | Hexahydroazepines |
| JPS4911844A (it) * | 1972-05-09 | 1974-02-01 | ||
| BE850777A (fr) * | 1976-01-28 | 1977-07-26 | Sandoz Sa | Nouveaux derives de la pyrrolidine |
-
1977
- 1977-12-22 GB GB53370/77A patent/GB1593888A/en not_active Expired
-
1978
- 1978-05-30 CY CY1144A patent/CY1144A/en unknown
- 1978-05-30 CY CY1145A patent/CY1145A/en unknown
- 1978-11-06 ZA ZA786244A patent/ZA786244B/xx unknown
- 1978-11-08 NZ NZ188863A patent/NZ188863A/xx unknown
- 1978-11-09 CA CA316,049A patent/CA1113092A/en not_active Expired
- 1978-11-09 CA CA316,048A patent/CA1113465A/en not_active Expired
- 1978-11-10 IL IL55924A patent/IL55924A/xx unknown
- 1978-11-10 AU AU41479/78A patent/AU519653B2/en not_active Expired
- 1978-11-15 US US05/961,086 patent/US4197239A/en not_active Expired - Lifetime
- 1978-11-15 US US05/961,087 patent/US4197241A/en not_active Expired - Lifetime
- 1978-11-15 IE IE2252/78A patent/IE47631B1/en unknown
- 1978-11-20 IN IN1249/CAL/78A patent/IN150193B/en unknown
- 1978-11-28 AR AR274561A patent/AR221710A1/es active
- 1978-11-30 MX MX787562U patent/MX5628E/es unknown
- 1978-11-30 DK DK546578A patent/DK156302C/da not_active IP Right Cessation
- 1978-12-06 DE DE7878300753T patent/DE2862139D1/de not_active Expired
- 1978-12-06 EP EP78300753A patent/EP0003253B1/en not_active Expired
- 1978-12-08 PH PH21913A patent/PH14412A/en unknown
- 1978-12-08 PH PH21914A patent/PH14517A/en unknown
- 1978-12-15 AT AT0898578A patent/AT373586B/de not_active IP Right Cessation
- 1978-12-19 YU YU2997/78A patent/YU40543B/xx unknown
- 1978-12-19 GR GR57927A patent/GR64029B/el unknown
- 1978-12-20 DD DD78209990A patent/DD141308A5/de unknown
- 1978-12-20 SU SU782699100A patent/SU1301311A3/ru active
- 1978-12-20 ES ES476160A patent/ES476160A1/es not_active Expired
- 1978-12-20 DD DD78219713A patent/DD149515A5/de unknown
- 1978-12-20 PL PL1978211970A patent/PL126008B1/pl unknown
- 1978-12-20 EG EG724/78A patent/EG13745A/xx active
- 1978-12-20 FI FI783922A patent/FI70575C/fi not_active IP Right Cessation
- 1978-12-21 PT PT68962A patent/PT68962A/pt unknown
- 1978-12-21 HU HU78WI298A patent/HU181997B/hu unknown
- 1978-12-21 JP JP15695778A patent/JPS5488286A/ja active Granted
- 1978-12-21 CS CS788756A patent/CS207748B2/cs unknown
- 1978-12-22 IT IT31286/78A patent/IT1102761B/it active
-
1979
- 1979-05-31 ES ES481125A patent/ES481125A1/es not_active Expired
-
1982
- 1982-04-06 KE KE3206A patent/KE3206A/xx unknown
- 1982-04-06 KE KE3207A patent/KE3207A/xx unknown
- 1982-04-29 HK HK180/82A patent/HK18082A/xx not_active IP Right Cessation
- 1982-04-29 HK HK181/82A patent/HK18182A/en not_active IP Right Cessation
- 1982-12-30 MY MY279/82A patent/MY8200279A/xx unknown
- 1982-12-30 MY MY278/82A patent/MY8200278A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3014911A (en) | Derivatives of dibenzo[a, e]cycloheptatriene | |
| Padwa et al. | Formation of polysubstituted 1, 2, 5, 6-tetrahydropyridines from the 4+ 2 cycloaddition reaction of bis (phenylsulfonyl) butadienes with aryl imines | |
| CS207748B2 (en) | Method of making the derivatives of the hexahydroazepine,piperidine or pyrrolidine | |
| HU205116B (en) | Process for producing 1,4-diazabicyclo/3.2.2./nonane | |
| US3037986A (en) | 2-(para-methoxyphenylcarbinol)-1-(phenylalkyl) piperidinium hydrobromide | |
| US3103513A (en) | Process for preparing hexadehy- | |
| US4296029A (en) | Process for preparing hexahydroazepine, piperidine and pyrrolidine derivatives | |
| NO157782B (no) | Analogifremgangsmte for fremstilling av terapeutisk aktive kondenserte as-triazinderivater med et pyridoringsystem hvor de to ringsystemer har et felles n-atom. | |
| NO131172B (it) | ||
| CA1295332C (en) | Hydropyridine derivatives | |
| US3792042A (en) | Dihydrodibenzo(b,f)azepine derivatives | |
| CA1105928A (en) | Hexahydroazepine piperidine and pyrrolidine derivatives | |
| EP0090203B1 (en) | Process for preparing p.chlorophenoxyacetyl-piperonylpiperazine | |
| US4463177A (en) | Process for making m-hydroxyphenyl substituted compounds | |
| JPH0225916B2 (it) | ||
| IE47632B1 (en) | Hexahydroazepine, piperidine and pyrrolidine derivatives | |
| KR820000717B1 (ko) | 헥사하이드로 아제핀, 피페리딘 및 피롤리딘 유도체의 제조방법 | |
| Snyder et al. | Amine Replacement Reactions of α-Dimethylaminomethyl-β-methoxynaphthalene | |
| GB1593889A (en) | Hexahydroazepine piperidine and pyrrolidine derivatives | |
| Part et al. | Scheme | |
| GB2113676A (en) | m-Hydroxyphenyl substituted compounds | |
| JPH051259B2 (it) | ||
| JPS5950677B2 (ja) | ビス（ε−カプロラクチム）二塩化第二スズの製法 | |
| SE192261C1 (it) | ||
| JPH02138171A (ja) | ラクタム誘導体 |