CY1144A - Hexahydroazepine piperidine and pyrrolidine derivatives - Google Patents

Hexahydroazepine piperidine and pyrrolidine derivatives Download PDF

Info

Publication number: CY1144A
Authority: CY; Cyprus
Prior art keywords: compound; general formula; alkyl; hydrogen; aryl
Prior art date: 1977-12-22

Application number

CY1144A

Other languages

English (en)

Original Assignee

Wyeth John & Brother Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1977-12-22

Filing date

1978-05-30

Publication date

1982-09-10

1978-05-30 Application filed by Wyeth John & Brother Ltd filed Critical Wyeth John & Brother Ltd

1982-09-10 Publication of CY1144A publication Critical patent/CY1144A/en

Links

150000003235 pyrrolidines Chemical class 0.000 title description 5
SEDKBOTUUIWCQC-UHFFFAOYSA-N azepane;piperidine Chemical compound C1CCNCC1.C1CCCNCC1 SEDKBOTUUIWCQC-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 97
125000000217 alkyl group Chemical group 0.000 claims description 49
239000001257 hydrogen Substances 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 29
238000000034 method Methods 0.000 claims description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 19
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
229910052744 lithium Inorganic materials 0.000 claims description 12
-1 3 - oxocyclohexen 3 - (3 - oxocyclohexen - 1 - yl) - 2 - piperidone Chemical compound 0.000 claims description 10
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 10
150000002431 hydrogen Chemical group 0.000 claims description 9
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 claims description 8
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
229910052794 bromium Inorganic materials 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 8
239000011591 potassium Substances 0.000 claims description 8
229910052708 sodium Inorganic materials 0.000 claims description 8
239000011734 sodium Substances 0.000 claims description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 6
238000011065 in-situ storage Methods 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
230000002152 alkylating effect Effects 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000000596 cyclohexenyl group Chemical class C1(=CCCCC1)* 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
239000011630 iodine Substances 0.000 claims description 3
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 claims description 2
101100277337 Arabidopsis thaliana DDM1 gene Proteins 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
101150113676 chr1 gene Proteins 0.000 claims description 2
FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
150000003951 lactams Chemical class 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
WLOAVMARPXBGDJ-UHFFFAOYSA-N 1-benzyl-3-(3-oxocyclohexen-1-yl)azepan-2-one Chemical compound O=C1CCCC(C2C(N(CC=3C=CC=CC=3)CCCC2)=O)=C1 WLOAVMARPXBGDJ-UHFFFAOYSA-N 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
239000000203 mixture Substances 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000002904 solvent Substances 0.000 description 11
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
229940043279 diisopropylamine Drugs 0.000 description 7
239000007787 solid Substances 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical group [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
JBKVHLHDHHXQEQ-UHFFFAOYSA-N Caprolactam Natural products O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
JFTPIEHHCQPVCS-UHFFFAOYSA-N 3-methoxycyclohex-2-en-1-one Chemical compound COC1=CC(=O)CCC1 JFTPIEHHCQPVCS-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
ZWXPDGCFMMFNRW-UHFFFAOYSA-N N-methylcaprolactam Chemical compound CN1CCCCCC1=O ZWXPDGCFMMFNRW-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000000284 extract Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000000463 material Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
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
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
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-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
125000004432 carbon atom Chemical group C* 0.000 description 2
238000001816 cooling Methods 0.000 description 2
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
XUWHAWMETYGRKB-UHFFFAOYSA-N delta-valerolactam Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
HNJBEVLQSNELDL-UHFFFAOYSA-N gamma-butyrolactam Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000007788 liquid Substances 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
125000004433 nitrogen atom Chemical group N* 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
DJGIITKNTHQYPX-UHFFFAOYSA-N 1-benzylazepan-2-one Chemical compound O=C1CCCCCN1CC1=CC=CC=C1 DJGIITKNTHQYPX-UHFFFAOYSA-N 0.000 description 1
RPVBFFYNFVTCBX-UHFFFAOYSA-N 1-trimethylsilylazepan-2-one Chemical compound C[Si](C)(C)N1CCCCCC1=O RPVBFFYNFVTCBX-UHFFFAOYSA-N 0.000 description 1
UAMXXKRCPLMMPO-UHFFFAOYSA-N 2,3,3-trimethylpentan-2-amine Chemical compound CCC(C)(C)C(C)(C)N UAMXXKRCPLMMPO-UHFFFAOYSA-N 0.000 description 1
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 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-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
WJWVOTIDIAUGAR-UHFFFAOYSA-N 2-propan-2-yloxycyclohex-2-en-1-one Chemical compound CC(C)OC1=CCCCC1=O WJWVOTIDIAUGAR-UHFFFAOYSA-N 0.000 description 1
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 1
TWJZVJYUCAHEGB-UHFFFAOYSA-N 3-ethyl-1-methylazepan-2-one Chemical compound CCC1CCCCN(C)C1=O TWJZVJYUCAHEGB-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
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
241000276683 Caranx Species 0.000 description 1
229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
241001522296 Erithacus rubecula Species 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000001347 alkyl bromides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
229960003280 cupric chloride Drugs 0.000 description 1
150000001923 cyclic compounds Chemical class 0.000 description 1
238000005661 deetherification reaction Methods 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
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
210000002196 fr. b Anatomy 0.000 description 1
210000003918 fraction a Anatomy 0.000 description 1
238000001030 gas--liquid chromatography Methods 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002366 halogen compounds Chemical class 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
238000007871 hydride transfer reaction Methods 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
JVIROGFHRRKAPE-UHFFFAOYSA-N lithium di(propan-2-yl)azanide 3-(3-oxocyclohexen-1-yl)azepan-2-one Chemical compound C(C)(C)[N-]C(C)C.[Li+].O=C1C=C(CCC1)C1C(NCCCC1)=O JVIROGFHRRKAPE-UHFFFAOYSA-N 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
JLICHNCFTLFZJN-HNNXBMFYSA-N meptazinol Chemical compound C=1C=CC(O)=CC=1[C@@]1(CC)CCCCN(C)C1 JLICHNCFTLFZJN-HNNXBMFYSA-N 0.000 description 1
229960000365 meptazinol Drugs 0.000 description 1
150000002736 metal compounds Chemical class 0.000 description 1
229950009273 myfadol Drugs 0.000 description 1
UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000011368 organic material Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
229950004859 profadol Drugs 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229940083608 sodium hydroxide Drugs 0.000 description 1
235000011121 sodium hydroxide Nutrition 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

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)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pain & Pain Management (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (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)
Other In-Based Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

CY1144A 1977-12-22 1978-05-30 Hexahydroazepine piperidine and pyrrolidine derivatives CY1144A (en)

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
CY1144A true CY1144A (en)	1982-09-10

Family

ID=10467561

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CY1144A CY1144A (en)	1977-12-22	1978-05-30	Hexahydroazepine piperidine and pyrrolidine derivatives
CY1145A CY1145A (en)	1977-12-22	1978-05-30	Hexahydroazepine piperidine and pyrrolidine derivatives

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CY1145A CY1145A (en)	1977-12-22	1978-05-30	Hexahydroazepine piperidine and pyrrolidine derivatives

Country Status (33)

Country	Link
US (2)	US4197239A (da)
EP (1)	EP0003253B1 (da)
JP (1)	JPS5488286A (da)
AR (1)	AR221710A1 (da)
AT (1)	AT373586B (da)
AU (1)	AU519653B2 (da)
CA (2)	CA1113092A (da)
CS (1)	CS207748B2 (da)
CY (2)	CY1144A (da)
DD (2)	DD141308A5 (da)
DE (1)	DE2862139D1 (da)
DK (1)	DK156302C (da)
EG (1)	EG13745A (da)
ES (2)	ES476160A1 (da)
FI (1)	FI70575C (da)
GB (1)	GB1593888A (da)
GR (1)	GR64029B (da)
HK (2)	HK18182A (da)
HU (1)	HU181997B (da)
IE (1)	IE47631B1 (da)
IL (1)	IL55924A (da)
IN (1)	IN150193B (da)
IT (1)	IT1102761B (da)
KE (2)	KE3207A (da)
MX (1)	MX5628E (da)
MY (2)	MY8200278A (da)
NZ (1)	NZ188863A (da)
PH (2)	PH14412A (da)
PL (1)	PL126008B1 (da)
PT (1)	PT68962A (da)
SU (1)	SU1301311A3 (da)
YU (1)	YU40543B (da)
ZA (1)	ZA786244B (da)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
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
RU2378258C2 (ru) *	2004-07-13	2010-01-10	Ф. Хоффманн-Ля Рош Аг	Производные сульфонамида

Family Cites Families (11)

* Cited by examiner, † Cited by third party
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 (da) *	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
CH526535A (de) *	1970-02-05	1972-08-15	Sandoz Ag	Verfahren zur Herstellung neuer Pyrrolidin-1-carboxamidinderivate
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
US3729465A (en) *	1971-02-03	1973-04-24	Wyeth John & Brother Ltd	Hexahydroazepines
JPS4911844A (da) *	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 AU AU41479/78A patent/AU519653B2/en not_active Expired
- 1978-11-10 IL IL55924A patent/IL55924A/xx unknown
- 1978-11-15 US US05/961,086 patent/US4197239A/en not_active Expired - Lifetime
- 1978-11-15 IE IE2252/78A patent/IE47631B1/en unknown
- 1978-11-15 US US05/961,087 patent/US4197241A/en not_active Expired - Lifetime
- 1978-11-20 IN IN1249/CAL/78A patent/IN150193B/en unknown
- 1978-11-28 AR AR274561A patent/AR221710A1/es active
- 1978-11-30 DK DK546578A patent/DK156302C/da not_active IP Right Cessation
- 1978-11-30 MX MX787562U patent/MX5628E/es unknown
- 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 GR GR57927A patent/GR64029B/el unknown
- 1978-12-19 YU YU2997/78A patent/YU40543B/xx unknown
- 1978-12-20 EG EG724/78A patent/EG13745A/xx active
- 1978-12-20 PL PL1978211970A patent/PL126008B1/pl unknown
- 1978-12-20 DD DD78209990A patent/DD141308A5/de unknown
- 1978-12-20 DD DD78219713A patent/DD149515A5/de unknown
- 1978-12-20 SU SU782699100A patent/SU1301311A3/ru active
- 1978-12-20 FI FI783922A patent/FI70575C/fi not_active IP Right Cessation
- 1978-12-20 ES ES476160A patent/ES476160A1/es not_active Expired
- 1978-12-21 JP JP15695778A patent/JPS5488286A/ja active Granted
- 1978-12-21 PT PT68962A patent/PT68962A/pt unknown
- 1978-12-21 HU HU78WI298A patent/HU181997B/hu unknown
- 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 KE3207A patent/KE3207A/xx unknown
- 1982-04-06 KE KE3206A patent/KE3206A/xx unknown
- 1982-04-29 HK HK181/82A patent/HK18182A/en not_active IP Right Cessation
- 1982-04-29 HK HK180/82A patent/HK18082A/xx not_active IP Right Cessation
- 1982-12-30 MY MY278/82A patent/MY8200278A/xx unknown
- 1982-12-30 MY MY279/82A patent/MY8200279A/xx unknown

Also Published As

Publication number	Publication date
CS207748B2 (en)	1981-08-31
SU1301311A3 (ru)	1987-03-30
MX5628E (es)	1983-11-15
PH14517A (en)	1981-08-26
KE3207A (en)	1982-05-21
CA1113465A (en)	1981-12-01
IT7831286A0 (it)	1978-12-22
PT68962A (en)	1979-01-01
IL55924A0 (en)	1979-01-31
US4197239A (en)	1980-04-08
IN150193B (da)	1982-08-14
DK156302C (da)	1989-12-11
DD141308A5 (de)	1980-04-23
PH14412A (en)	1981-07-09
HK18082A (en)	1982-05-07
ZA786244B (en)	1980-06-25
FI70575B (fi)	1986-06-06
FI783922A7 (fi)	1979-06-23
DD149515A5 (de)	1981-07-15
IT1102761B (it)	1985-10-07
GB1593888A (en)	1981-07-22
AU4147978A (en)	1979-06-28
MY8200279A (en)	1982-12-31
ES476160A1 (es)	1979-11-16
PL126008B1 (en)	1983-06-30
JPS64392B2 (da)	1989-01-06
NZ188863A (en)	1982-03-16
EP0003253B1 (en)	1982-12-22
HU181997B (en)	1983-11-28
EG13745A (en)	1983-03-31
YU299778A (en)	1983-12-31
AT373586B (de)	1984-02-10
GR64029B (en)	1980-01-19
FI70575C (fi)	1986-09-24
IE47631B1 (en)	1984-05-16
ES481125A1 (es)	1980-02-01
ATA898578A (de)	1983-06-15
JPS5488286A (en)	1979-07-13
MY8200278A (en)	1982-12-31
DK546578A (da)	1979-06-23
YU40543B (en)	1986-02-28
US4197241A (en)	1980-04-08
AU519653B2 (en)	1981-12-17
CA1113092A (en)	1981-11-24
PL211970A1 (da)	1980-02-25
DK156302B (da)	1989-07-31
HK18182A (en)	1982-05-07
AR221710A1 (es)	1981-03-13
DE2862139D1 (en)	1983-01-27
IL55924A (en)	1982-01-31
KE3206A (en)	1982-05-21
IE782252L (en)	1979-06-22
CY1145A (en)	1982-09-10
EP0003253A1 (en)	1979-08-08

Publication	Publication Date	Title
US4115400A (en)	1978-09-19	1-Azoniabicyclo[3.1.0]hexanes
US4081450A (en)	1978-03-28	1,3,4-Trisubstituted-4-arylpiperidines and their preparation
US4191771A (en)	1980-03-04	Analgesic method using 1,3,4-trisubstituted-4-arylpiperidines
NZ272704A (en)	1997-02-24	2-iodobenzene sulphonylurea derivatives and analogues
US4197241A (en)	1980-04-08	Hexahydroazepine, piperidine and pyrrolidine derivatives
US6197976B1 (en)	2001-03-06	Preparation of ketorolac
EP0021552B1 (en)	1983-01-26	Hexahydroazepine, piperidine and pyrrolidine derivatives and processes for preparing them
US4251659A (en)	1981-02-17	Polyfluorohydroxyisopropyl-heterocyclic compounds
EP0021772B1 (en)	1985-01-02	Method of preparing 2-oxo- and 2-unsubstituted-hexahydroazepine derivatives
US4463177A (en)	1984-07-31	Process for making m-hydroxyphenyl substituted compounds
US5446162A (en)	1995-08-29	Process for the production of 7-acylindoles
US4175197A (en)	1979-11-20	1,3,4-Trisubstituted-4-aryl-1,4,5,6-tetra-hydropyridines
CA1105929A (en)	1981-07-28	Hexahydroazepine piperidine and pyrrolidine derivatives
GB2113676A (en)	1983-08-10	m-Hydroxyphenyl substituted compounds
KR820000718B1 (ko)	1982-04-30	2-옥소-헥사하이드로 아제핀, 피페리딘 및 피롤리딘 유도체의 제조방법
GB1593889A (en)	1981-07-22	Hexahydroazepine piperidine and pyrrolidine derivatives
GB2145089A (en)	1985-03-20	Pyrrolidones, piperidones and hexahydroazepinones
US3627771A (en)	1971-12-14	Ring closure with cyanogen bromide
IE47632B1 (en)	1984-05-16	Hexahydroazepine, piperidine and pyrrolidine derivatives
EP0131921A2 (en)	1985-01-23	Ortho-(mono-substituted amino)phenylimines and production thereof
Kiricojević et al.	1996	JSeee ee
JPH051259B2 (da)	1993-01-07
NZ222517A (en)	1991-04-26	1-benzooxacycloalkylpyridine carboxylic acid derivatives, intermediates, and pharmaceutical compositions
GB2122629A (en)	1984-01-18	Novel silyl derivatives