DK141401B - Analogifremgangsmåde til fremstilling af hexahydro-1H-azepinforbindelser eller syreadditions- eller kvaternære ammoniumsalte deraf. - Google Patents

Analogifremgangsmåde til fremstilling af hexahydro-1H-azepinforbindelser eller syreadditions- eller kvaternære ammoniumsalte deraf. Download PDF

Info

Publication number: DK141401B
Authority: DK; Denmark
Prior art keywords: azepine; hexahydro; ethyl; hydroxyphenyl; ether
Prior art date: 1968-08-16

Application number

DK439969AA

Other languages

Danish (da)

English (en)

Other versions

DK141401C (no

Inventor

John Frederick Cavalla

Alan Chapman White

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.)

1968-08-16

Filing date

1969-08-15

Publication date

1980-03-10

1969-01-28 Priority claimed from GB4694/69A external-priority patent/GB1285025A/en

1969-08-15 Application filed by Wyeth John & Brother Ltd filed Critical Wyeth John & Brother Ltd

1980-03-10 Publication of DK141401B publication Critical patent/DK141401B/da

1980-09-08 Application granted granted Critical

1980-09-08 Publication of DK141401C publication Critical patent/DK141401C/da

Links

ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical class C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 title claims description 25
239000002253 acid Substances 0.000 title claims description 19
150000003242 quaternary ammonium salts Chemical class 0.000 title claims description 7
238000004519 manufacturing process Methods 0.000 title description 2
238000000034 method Methods 0.000 claims description 38
125000000217 alkyl group Chemical group 0.000 claims description 32
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 13
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 9
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 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 6
125000002252 acyl group Chemical group 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
125000001188 haloalkyl group Chemical group 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 143
-1 m-hydroxyphenyl Chemical group 0.000 description 104
150000001875 compounds Chemical class 0.000 description 96
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 63
239000000047 product Substances 0.000 description 62
239000000203 mixture Substances 0.000 description 60
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
229910052739 hydrogen Inorganic materials 0.000 description 53
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
239000003921 oil Substances 0.000 description 45
239000000243 solution Substances 0.000 description 45
239000001257 hydrogen Substances 0.000 description 44
235000019198 oils Nutrition 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 40
238000010992 reflux Methods 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 38
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
230000002829 reductive effect Effects 0.000 description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-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 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
238000009835 boiling Methods 0.000 description 24
238000004458 analytical method Methods 0.000 description 23
229910000042 hydrogen bromide Inorganic materials 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
239000002904 solvent Substances 0.000 description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
238000001704 evaporation Methods 0.000 description 19
229910000027 potassium carbonate Inorganic materials 0.000 description 19
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
230000000202 analgesic effect Effects 0.000 description 16
230000008020 evaporation Effects 0.000 description 16
235000019441 ethanol Nutrition 0.000 description 15
150000002431 hydrogen Chemical class 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
238000001953 recrystallisation Methods 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
239000012230 colorless oil Substances 0.000 description 12
230000000694 effects Effects 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
229910000041 hydrogen chloride Inorganic materials 0.000 description 11
239000012044 organic layer Substances 0.000 description 11
229910052708 sodium Inorganic materials 0.000 description 11
239000011734 sodium Substances 0.000 description 11
239000000725 suspension Substances 0.000 description 11
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 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
238000001035 drying Methods 0.000 description 10
SRKPTFLLCFBPCD-UHFFFAOYSA-N 3-(3-ethylazepan-3-yl)phenol Chemical compound C=1C=CC(O)=CC=1C1(CC)CCCCNC1 SRKPTFLLCFBPCD-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
125000001589 carboacyl group Chemical group 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
239000012280 lithium aluminium hydride Substances 0.000 description 9
239000000463 material Substances 0.000 description 9
230000009467 reduction Effects 0.000 description 9
238000006722 reduction reaction Methods 0.000 description 9
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
241000700159 Rattus Species 0.000 description 8
239000002585 base Substances 0.000 description 8
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000010410 layer Substances 0.000 description 8
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 8
238000012360 testing method Methods 0.000 description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 6
235000011114 ammonium hydroxide Nutrition 0.000 description 6
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 6
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 6
238000004821 distillation Methods 0.000 description 6
JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 5
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 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
239000008896 Opium Substances 0.000 description 5
SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 5
229960004415 codeine phosphate Drugs 0.000 description 5
229960004193 dextropropoxyphene Drugs 0.000 description 5
XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000012458 free base Substances 0.000 description 5
239000011521 glass Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
229960001027 opium Drugs 0.000 description 5
230000000144 pharmacologic effect Effects 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 4
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 4
UWULSBBGFGMBHN-UHFFFAOYSA-N 3-ethyl-3-(3-methoxyphenyl)azepane Chemical compound C=1C=CC(OC)=CC=1C1(CC)CCCCNC1 UWULSBBGFGMBHN-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
230000003042 antagnostic effect Effects 0.000 description 4
230000002920 convulsive effect Effects 0.000 description 4
WGJHHMKQBWSQIY-UHFFFAOYSA-N ethoheptazine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCCN(C)CC1 WGJHHMKQBWSQIY-UHFFFAOYSA-N 0.000 description 4
RLZFVPPGVAHZPE-UHFFFAOYSA-N ethyl 4-iodobutanoate Chemical compound CCOC(=O)CCCI RLZFVPPGVAHZPE-UHFFFAOYSA-N 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
229910010272 inorganic material Inorganic materials 0.000 description 4
239000011147 inorganic material Substances 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
229960005181 morphine Drugs 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 3
JKXQKGNGJVZKFA-UHFFFAOYSA-N 1-chloro-3-methylbut-2-ene Chemical compound CC(C)=CCCl JKXQKGNGJVZKFA-UHFFFAOYSA-N 0.000 description 3
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 3
CQCJMDQJCYEDMN-UHFFFAOYSA-N 3-(1-methyl-3-propylazepan-3-yl)phenol Chemical compound OC=1C=C(C=CC1)C1(CN(CCCC1)C)CCC CQCJMDQJCYEDMN-UHFFFAOYSA-N 0.000 description 3
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 3
PXPZNNKGVBRBFZ-UHFFFAOYSA-N 3-(3-methoxyphenyl)-3-propylazepane Chemical compound COC=1C=C(C=CC1)C1(CNCCCC1)CCC PXPZNNKGVBRBFZ-UHFFFAOYSA-N 0.000 description 3
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
CWINCVBWHUGBEB-UHFFFAOYSA-N 4-iodobutanenitrile Chemical compound ICCCC#N CWINCVBWHUGBEB-UHFFFAOYSA-N 0.000 description 3
USJKZWMWMYWDRB-UHFFFAOYSA-N 6-(3-methoxyphenyl)-6-propylazepan-2-one Chemical compound COC=1C=C(C=CC1)C1(CCCC(NC1)=O)CCC USJKZWMWMYWDRB-UHFFFAOYSA-N 0.000 description 3
DLLAYTSJCIEZBS-UHFFFAOYSA-N 6-ethyl-6-(3-methoxyphenyl)azepan-2-one Chemical compound C=1C=CC(OC)=CC=1C1(CC)CCCC(=O)NC1 DLLAYTSJCIEZBS-UHFFFAOYSA-N 0.000 description 3
GVARWTBONJFEKX-UHFFFAOYSA-N Br.C(C)C1(CNCCCC1)C1=CC(=CC=C1)O Chemical compound Br.C(C)C1(CNCCCC1)C1=CC(=CC=C1)O GVARWTBONJFEKX-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical class [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
150000008041 alkali metal carbonates Chemical class 0.000 description 3
DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
229960004126 codeine Drugs 0.000 description 3
238000001816 cooling Methods 0.000 description 3
229960000569 ethoheptazine Drugs 0.000 description 3
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OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
230000036407 pain Effects 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 3
230000007017 scission Effects 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000007858 starting material Substances 0.000 description 3
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 3
GNHGSSSQCHAIEL-UHFFFAOYSA-N 1h-azepine;hydrobromide Chemical compound Br.N1C=CC=CC=C1 GNHGSSSQCHAIEL-UHFFFAOYSA-N 0.000 description 2
CIDTUGIPHMXGPB-UHFFFAOYSA-N 2-(3-methoxyphenyl)butanenitrile Chemical compound CCC(C#N)C1=CC=CC(OC)=C1 CIDTUGIPHMXGPB-UHFFFAOYSA-N 0.000 description 2
IHCLZIIKZFCPJD-UHFFFAOYSA-N 2-(3-methoxyphenyl)propanenitrile Chemical compound COC1=CC=CC(C(C)C#N)=C1 IHCLZIIKZFCPJD-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
AAQIQEALLIPJHH-UHFFFAOYSA-N 3-[1-(cyclopropylmethyl)-3-ethylazepan-3-yl]phenol Chemical compound C1C(CC)(C=2C=C(O)C=CC=2)CCCCN1CC1CC1 AAQIQEALLIPJHH-UHFFFAOYSA-N 0.000 description 2
QAJNFWHNFJLKTA-UHFFFAOYSA-N 6-(3-methoxyphenyl)-6-methylazepan-2-one Chemical compound COC=1C=C(C=CC=1)C1(CCCC(NC1)=O)C QAJNFWHNFJLKTA-UHFFFAOYSA-N 0.000 description 2
206010010774 Constipation Diseases 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
230000037023 motor activity Effects 0.000 description 1
230000003533 narcotic effect Effects 0.000 description 1
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239000012299 nitrogen atmosphere Substances 0.000 description 1
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KDLHZDBZIXYQEI-VENIDDJXSA-N palladium-100 Chemical compound [100Pd] KDLHZDBZIXYQEI-VENIDDJXSA-N 0.000 description 1
230000037361 pathway Effects 0.000 description 1
VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
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QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
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QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
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229940095064 tartrate Drugs 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000563 toxic property Toxicity 0.000 description 1
NRTLTGGGUQIRRT-UHFFFAOYSA-N triethylazanium;bromide Chemical compound [Br-].CC[NH+](CC)CC NRTLTGGGUQIRRT-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (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)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

DK439969AA 1968-08-16 1969-08-15 Analogifremgangsmåde til fremstilling af hexahydro-1H-azepinforbindelser eller syreadditions- eller kvaternære ammoniumsalte deraf. DK141401B (da)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GB3920168		1968-08-16
GB3920168		1968-08-16
GB4206068		1968-09-04
GB4206068		1968-09-04
GB4694/69A GB1285025A (en)	1968-08-16	1969-01-28	Hexahydroazepines
GB469469		1969-01-28

Publications (2)

Publication Number	Publication Date
DK141401B true DK141401B (da)	1980-03-10
DK141401C DK141401C (no)	1980-09-08

Family

ID=27254483

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
DK439969AA DK141401B (da)	1968-08-16	1969-08-15	Analogifremgangsmåde til fremstilling af hexahydro-1H-azepinforbindelser eller syreadditions- eller kvaternære ammoniumsalte deraf.
DK340571A DK150849C (da)	1968-08-16	1971-07-09	Hexahydro-2h-azepin-2-oner til anvendelse som mellemprodukter ved fremstilling af hexahydro-1h-azepinderivater eller et syreadditionssalt eller kvaternaert ammoniumsalt deraf

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
DK340571A DK150849C (da)	1968-08-16	1971-07-09	Hexahydro-2h-azepin-2-oner til anvendelse som mellemprodukter ved fremstilling af hexahydro-1h-azepinderivater eller et syreadditionssalt eller kvaternaert ammoniumsalt deraf

Country Status (18)

Country	Link
JP (1)	JPS505197B1 (no)
AR (1)	AR194353A1 (no)
AT (1)	AT312611B (no)
BE (1)	BE737548A (no)
CH (3)	CH554864A (no)
DE (1)	DE1941534C3 (no)
DK (2)	DK141401B (no)
ES (1)	ES370497A1 (no)
FI (1)	FI51479C (no)
FR (1)	FR2015812A1 (no)
HU (1)	HU162512B (no)
IE (1)	IE33382B1 (no)
IL (1)	IL32801A (no)
IT (1)	IT1053698B (no)
NL (1)	NL164275C (no)
NO (2)	NO132046C (no)
SE (1)	SE366043B (no)
YU (2)	YU34124B (no)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1319785A (en) *	1970-02-06	1973-06-06	Wyeth John & Brother Ltd	Hexahydroazepines
US3666752A (en) *	1970-03-09	1972-05-30	Bristol Myers Co	4,4-diphenylhexahydroazepine compounds
DE2901180A1 (de) *	1979-01-13	1980-07-24	Basf Ag	Hexahydro-1,4-oxazepine, verfahren zu deren herstellung und diese enthaltende arzneimittel
SE439186B (sv) *	1980-12-04	1985-06-03	Olof Ohrnell	Elastisk koppling mellan ett inre och ett yttre i forhallande till varandra koncentriska ror
DE3502667A1 (de) *	1985-01-26	1986-07-31	Klöckner-Humboldt-Deutz AG, 5000 Köln	Oelschleuderfilter fuer brennkraftmaschinen
JPWO2005037269A1 (ja) *	2003-10-21	2006-12-28	住友製薬株式会社	新規ピペリジン誘導体
WO2017121645A1 (en) *	2016-01-15	2017-07-20	Laboratorios Del Dr. Esteve, S.A.	3-ethyl-3-phenylazepane derivatives having multimodal activity against pain

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2740779A (en) *		1956-04-03		Substituted azacycloalkanes

1969
- 1969-08-06 IE IE1102/69A patent/IE33382B1/xx unknown
- 1969-08-08 IL IL32801A patent/IL32801A/xx unknown
- 1969-08-14 BE BE737548D patent/BE737548A/xx not_active IP Right Cessation
- 1969-08-14 IT IT20967/69A patent/IT1053698B/it active
- 1969-08-14 DE DE1941534A patent/DE1941534C3/de not_active Expired
- 1969-08-14 ES ES370497A patent/ES370497A1/es not_active Expired
- 1969-08-14 FR FR6928129A patent/FR2015812A1/fr not_active Withdrawn
- 1969-08-15 HU HUWI160A patent/HU162512B/hu unknown
- 1969-08-15 FI FI692393A patent/FI51479C/fi active
- 1969-08-15 JP JP44064669A patent/JPS505197B1/ja active Pending
- 1969-08-15 CH CH1056472A patent/CH554864A/xx not_active IP Right Cessation
- 1969-08-15 YU YU2102/69A patent/YU34124B/xx unknown
- 1969-08-15 SE SE11395/69A patent/SE366043B/xx unknown
- 1969-08-15 CH CH340773A patent/CH554865A/xx not_active IP Right Cessation
- 1969-08-15 NL NL6912483.A patent/NL164275C/xx not_active IP Right Cessation
- 1969-08-15 CH CH1241969A patent/CH536843A/de not_active IP Right Cessation
- 1969-08-15 DK DK439969AA patent/DK141401B/da not_active IP Right Cessation
- 1969-08-15 NO NO3311/69A patent/NO132046C/no unknown
- 1969-08-18 AT AT789269A patent/AT312611B/de not_active IP Right Cessation
1971
- 1971-07-09 DK DK340571A patent/DK150849C/da not_active IP Right Cessation
- 1971-11-30 AR AR239343A patent/AR194353A1/es active
1975
- 1975-02-11 NO NO750442A patent/NO142395C/no unknown
- 1975-10-27 YU YU02716/75A patent/YU39170B/xx unknown

Also Published As

Publication number	Publication date
NO132046C (no)	1975-09-10
IL32801A (en)	1973-06-29
AT312611B (de)	1974-01-10
YU39170B (en)	1984-08-31
SE366043B (no)	1974-04-08
DE1941534B2 (de)	1979-11-15
FI51479B (no)	1976-09-30
BE737548A (no)	1970-02-16
IT1053698B (it)	1981-10-10
DK141401C (no)	1980-09-08
NO132046B (no)	1975-06-02
NO750442L (no)	1970-02-17
DK150849B (da)	1987-07-06
FI51479C (fi)	1977-01-10
JPS505197B1 (no)	1975-02-28
IE33382L (en)	1970-02-16
NL164275B (nl)	1980-07-15
ES370497A1 (es)	1972-04-16
CH554865A (de)	1974-10-15
NL6912483A (no)	1970-02-18
YU271675A (en)	1982-02-28
NL164275C (nl)	1980-12-15
DE1941534C3 (de)	1980-07-24
NO142395C (no)	1980-08-13
IE33382B1 (en)	1974-06-12
IL32801A0 (en)	1969-11-12
HU162512B (no)	1973-02-28
FR2015812A1 (en)	1970-04-30
NO142395B (no)	1980-05-05
YU34124B (en)	1978-12-31
DE1941534A1 (de)	1970-04-09
YU210269A (en)	1978-06-30
CH554864A (de)	1974-10-15
AR194353A1 (es)	1973-07-13
DK150849C (da)	1988-02-01
CH536843A (de)	1973-05-15

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EA007225B1 (ru)	2006-08-25	Производные n-[фенил(пиперидин-2-ил)метил]бензамида и их применение в терапии
NO164505B (no)	1990-07-02	Fremgangsmaate og apparat for undersoekelse av tilstanden for biologiske partikler.
JPH03173867A (ja)	1991-07-29	環状アミン化合物
NZ212856A (en)	1988-05-30	Glutarimide derivatives and pharmaceutical compositions
EP1274411A1 (en)	2003-01-15	Phenylethylamines and condensed rings variants as prodrugs of catecholamines, and their use
AU2001248982A1 (en)	2002-01-17	Phenylethylamines and condensed rings variants as prodrugs of catecholamines, and their use
DK148688B (da)	1985-09-02	Analogifremgangsmaade til fremstilling af basisk substituerede 7-alkylteofyllinderivater eller salte deraf med farmaceutisk acceptable syrer
FI62052C (fi)	1982-11-10	Foerfarande foer framstaellning av farmakologiskt vaerdefulla 4-aminofenyletanolaminer med saerskilt beta2-mimetisk och ala1-blockerande verkan
FI67371C (fi)	1985-03-11	Foerfarande foer framstaellning av nya farmakologiskt aktiva fenylazacykloalkaner
DK141401B (da)	1980-03-10	Analogifremgangsmåde til fremstilling af hexahydro-1H-azepinforbindelser eller syreadditions- eller kvaternære ammoniumsalte deraf.
Lunsford et al.	1964	4-(β-substituted ethyl)-3, 3-diphenyl-2-pyrrolidinones. A new series of CNS Stimulants1
EP0337167B1 (en)	1994-08-03	4-Aryl-4-piperidine (or pyrrolidine or hexahydroazepine) carbinols and heterocyclic analogs thereof
Bishop et al.	1968	Analgetics based on the azetidine ring
Allmendinger et al.	2012	Carry over of impurities: a detailed exemplification for glycopyrrolate (NVA237)
NO126371B (no)	1973-01-29
CS195652B2 (en)	1980-02-29	Method of producing new 4-diphenylmethylen-1-hydroxy-benzylpiperidines
KR910003711B1 (ko)	1991-06-08	2-(n-피롤리디노)-3-이소부톡시-n-치환된 페닐-n-벤질-프로필아민의 제조방법
US5086063A (en)	1992-02-04	4-aryl-4-piperidine (or pyrrolidine or hexahydroazepine) carbinols and heterocyclic analogs thereof
US3729465A (en)	1973-04-24	Hexahydroazepines
US4465834A (en)	1984-08-14	Anticholinergic drugs
Ong et al.	1978	Synthesis and analgetic activity of some 5-aryl-2-azabicyclo [3.2. 1] octanes
US5019650A (en)	1991-05-28	4-aryl-4-piperidine (or pyrrolidine or hexahydroazepine) carbinols and heterocyclic analogs thereof
US5109006A (en)	1992-04-28	Certain pharmaceutically active 6H-imidazo[1,2-a]pyridine-5-ones
DK150477B (da)	1987-03-09	Analogifremgangsmaade til fremstilling af 4-(4-(naphthalenyloxy)-1-piperidinyl)-1-phenyl-1-butanonderivater og mellemprodukter til brug ved fremgangsmaaden

Legal Events

Date	Code	Title	Description
1989-04-17	PBP	Patent lapsed