CA1133495A - Cis and trans-3-aryloxy-4- hydroxypyrrolidines and derivatives thereof - Google Patents
Cis and trans-3-aryloxy-4- hydroxypyrrolidines and derivatives thereofInfo
- Publication number
- CA1133495A CA1133495A CA343,328A CA343328A CA1133495A CA 1133495 A CA1133495 A CA 1133495A CA 343328 A CA343328 A CA 343328A CA 1133495 A CA1133495 A CA 1133495A
- Authority
- CA
- Canada
- Prior art keywords
- trans
- process according
- pyrrolidinol
- formula
- hydrogen
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 40
- 239000001257 hydrogen Substances 0.000 claims abstract description 39
- -1 loweralkyl Chemical group 0.000 claims abstract description 34
- 150000003839 salts Chemical group 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 41
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 25
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 23
- 239000002904 solvent Substances 0.000 claims description 23
- SOOHWZBGWRAMJJ-UHFFFAOYSA-N 3-benzyl-6-oxa-3-azabicyclo[3.1.0]hexane Chemical compound C1C2OC2CN1CC1=CC=CC=C1 SOOHWZBGWRAMJJ-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- WZDUNDJSSXEPAS-UHFFFAOYSA-N 3-ethyl-6-oxa-3-azabicyclo[3.1.0]hexane Chemical compound C1N(CC)CC2OC21 WZDUNDJSSXEPAS-UHFFFAOYSA-N 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 11
- 239000000376 reactant Substances 0.000 claims description 11
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 10
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 9
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 9
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 8
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 6
- 150000003891 oxalate salts Chemical class 0.000 claims description 6
- AJLQKQUQJWEGMJ-IAGOWNOFSA-N (3r,4r)-1-benzyl-4-phenoxypyrrolidin-3-ol Chemical compound C([C@H]([C@@H](C1)OC=2C=CC=CC=2)O)N1CC1=CC=CC=C1 AJLQKQUQJWEGMJ-IAGOWNOFSA-N 0.000 claims description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 229910001923 silver oxide Inorganic materials 0.000 claims description 5
- 239000012312 sodium hydride Substances 0.000 claims description 5
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 5
- AHQFGIPCABOHHT-HZPDHXFCSA-N (3r,4r)-1-benzyl-4-(2,6-dichlorophenoxy)pyrrolidin-3-ol Chemical compound C([C@H]([C@@H](C1)OC=2C(=CC=CC=2Cl)Cl)O)N1CC1=CC=CC=C1 AHQFGIPCABOHHT-HZPDHXFCSA-N 0.000 claims description 4
- HOLHYSJJBXSLMV-UHFFFAOYSA-N 2,6-dichlorophenol Chemical compound OC1=C(Cl)C=CC=C1Cl HOLHYSJJBXSLMV-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- MIFWKCCGJDJZPL-FOUVGRNNSA-M (3r,4r)-1-benzyl-1-methyl-4-phenoxypyrrolidin-1-ium-3-ol;iodide Chemical compound [I-].C([C@H]([C@H](O)C1)OC=2C=CC=CC=2)[N+]1(C)CC1=CC=CC=C1 MIFWKCCGJDJZPL-FOUVGRNNSA-M 0.000 claims description 3
- PBEDDLTYYGZKHB-VNYZMKMESA-N (3r,4r)-1-benzyl-4-(2,3-dichlorophenoxy)pyrrolidin-3-ol;hydrochloride Chemical compound Cl.C([C@H]([C@@H](C1)OC=2C(=C(Cl)C=CC=2)Cl)O)N1CC1=CC=CC=C1 PBEDDLTYYGZKHB-VNYZMKMESA-N 0.000 claims description 3
- KOYSMNHLBIJMFS-GHMZBOCLSA-N (3r,4r)-1-methyl-4-phenoxypyrrolidin-3-ol Chemical compound C1N(C)C[C@@H](O)[C@@H]1OC1=CC=CC=C1 KOYSMNHLBIJMFS-GHMZBOCLSA-N 0.000 claims description 3
- 101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 claims description 3
- UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical compound OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 7
- 239000000126 substance Substances 0.000 claims 7
- KIWWEIOFOPULSX-UHFFFAOYSA-N 6-oxa-3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2OC12 KIWWEIOFOPULSX-UHFFFAOYSA-N 0.000 claims 4
- 125000005059 halophenyl group Chemical group 0.000 claims 3
- LVMACDSVFPQQER-GDBMZVCRSA-N (3r,4r)-1-ethyl-4-naphthalen-1-yloxypyrrolidin-3-ol Chemical compound C1N(CC)C[C@@H](O)[C@@H]1OC1=CC=CC2=CC=CC=C12 LVMACDSVFPQQER-GDBMZVCRSA-N 0.000 claims 2
- XHMHZEARAIFOJZ-VXGBXAGGSA-N (3r,4r)-1-ethyl-4-phenoxypyrrolidin-3-ol Chemical compound C1N(CC)C[C@@H](O)[C@@H]1OC1=CC=CC=C1 XHMHZEARAIFOJZ-VXGBXAGGSA-N 0.000 claims 2
- PZKKEUJEOIHRBY-VXNVDRBHSA-N (3r,4r)-4-(2,3-dichlorophenoxy)pyrrolidin-3-ol Chemical compound O[C@@H]1CNC[C@H]1OC1=CC=CC(Cl)=C1Cl PZKKEUJEOIHRBY-VXNVDRBHSA-N 0.000 claims 2
- MYLHABWCUKUROP-GHMZBOCLSA-N (3r,4r)-4-(2,6-dichlorophenoxy)-1-ethylpyrrolidin-3-ol Chemical compound C1N(CC)C[C@@H](O)[C@@H]1OC1=C(Cl)C=CC=C1Cl MYLHABWCUKUROP-GHMZBOCLSA-N 0.000 claims 2
- ZXIDMMHTXZOWDR-RKDXNWHRSA-N (3r,4r)-4-(2,6-dichlorophenoxy)pyrrolidin-3-ol Chemical compound O[C@@H]1CNC[C@H]1OC1=C(Cl)C=CC=C1Cl ZXIDMMHTXZOWDR-RKDXNWHRSA-N 0.000 claims 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims 2
- 150000001350 alkyl halides Chemical class 0.000 claims 2
- 150000001351 alkyl iodides Chemical class 0.000 claims 2
- 238000005984 hydrogenation reaction Methods 0.000 claims 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims 2
- PRIYXVFZRRKLEK-UHFFFAOYSA-N 2-amino-1-(4-fluorophenyl)propan-1-one Chemical compound CC(N)C(=O)C1=CC=C(F)C=C1 PRIYXVFZRRKLEK-UHFFFAOYSA-N 0.000 claims 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 claims 1
- 229940107816 ammonium iodide Drugs 0.000 claims 1
- 238000007327 hydrogenolysis reaction Methods 0.000 claims 1
- JCZPOYAMKJFOLA-UHFFFAOYSA-N pyrrolidine-3,4-diol Chemical compound OC1CNCC1O JCZPOYAMKJFOLA-UHFFFAOYSA-N 0.000 claims 1
- 125000001453 quaternary ammonium group Chemical group 0.000 claims 1
- 230000001430 anti-depressive effect Effects 0.000 abstract description 8
- 239000000935 antidepressant agent Substances 0.000 abstract description 8
- 241001465754 Metazoa Species 0.000 abstract description 7
- 229940005513 antidepressants Drugs 0.000 abstract description 6
- 230000003288 anthiarrhythmic effect Effects 0.000 abstract description 4
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 154
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 92
- 239000000203 mixture Substances 0.000 description 86
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
- 238000004458 analytical method Methods 0.000 description 66
- 239000000243 solution Substances 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 44
- 239000000047 product Substances 0.000 description 38
- 239000003921 oil Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 239000007787 solid Substances 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 229960004132 diethyl ether Drugs 0.000 description 11
- 239000000725 suspension Substances 0.000 description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
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- 239000002585 base Substances 0.000 description 7
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- 150000002118 epoxides Chemical class 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 229910001873 dinitrogen Inorganic materials 0.000 description 5
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- DPHNJPUOMLRELT-UHFFFAOYSA-N 2,3-dihydro-1h-inden-4-ol Chemical compound OC1=CC=CC2=C1CCC2 DPHNJPUOMLRELT-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 206010003119 arrhythmia Diseases 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
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- 238000001704 evaporation Methods 0.000 description 4
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 4
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- 239000008101 lactose Substances 0.000 description 4
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
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- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
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- QJRIUWQPJVPYSO-UHFFFAOYSA-N 1-benzylpyrrolidine-3,4-diol Chemical compound C1C(O)C(O)CN1CC1=CC=CC=C1 QJRIUWQPJVPYSO-UHFFFAOYSA-N 0.000 description 2
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- JJBVQZMGJOHVOD-UHFFFAOYSA-N 4-(4-chlorophenoxy)pyrrolidin-3-ol Chemical compound OC1CNCC1OC1=CC=C(Cl)C=C1 JJBVQZMGJOHVOD-UHFFFAOYSA-N 0.000 description 2
- QXSAKPUBHTZHKW-UHFFFAOYSA-N 4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C=C1 QXSAKPUBHTZHKW-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- 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 2
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- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- VFGUZPZNOAEVCT-UHFFFAOYSA-L potassium sodium hydrogen sulfate hydroxide Chemical compound S(=O)(=O)([O-])O.[K+].[OH-].[Na+] VFGUZPZNOAEVCT-UHFFFAOYSA-L 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical class OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
- 150000003236 pyrrolines Chemical class 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- 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
- C07D207/10—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 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
- C07D207/12—Oxygen or sulfur atoms
-
- 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
- C07D207/20—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 only hydrogen 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)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US215179A | 1979-01-09 | 1979-01-09 | |
| US002,151 | 1979-01-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1133495A true CA1133495A (en) | 1982-10-12 |
Family
ID=21699450
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA343,328A Expired CA1133495A (en) | 1979-01-09 | 1980-01-09 | Cis and trans-3-aryloxy-4- hydroxypyrrolidines and derivatives thereof |
Country Status (9)
| Country | Link |
|---|---|
| JP (1) | JPS5598160A (en]) |
| CA (1) | CA1133495A (en]) |
| CH (1) | CH643243A5 (en]) |
| DE (1) | DE3000625A1 (en]) |
| FR (1) | FR2446279B1 (en]) |
| GB (1) | GB2040933B (en]) |
| IT (1) | IT1127967B (en]) |
| MX (1) | MX6634E (en]) |
| SE (1) | SE435927B (en]) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE45511B1 (en) | 1976-09-01 | 1982-09-08 | Ciba Geigy Ag | New derivatives of perhydro-aza-heterocycles and processesfor the production thereof |
| US4547514A (en) * | 1983-12-05 | 1985-10-15 | A. H. Robins Company, Incorporated | Aryloxy-N-(aminoalkyl)-1-pyrrolidine and piperidine carboxamides and carbothioamides having antiarrhythmic activity |
| JPS60178860A (ja) * | 1984-02-24 | 1985-09-12 | Sankyo Co Ltd | ３−メルカプトピロリジンまたはその塩の製法 |
| JPS6157552A (ja) * | 1984-08-29 | 1986-03-24 | Toyama Chem Co Ltd | ３−アミノピロリジンまたはその塩の製法 |
| DE3813416A1 (de) * | 1988-04-21 | 1989-11-02 | Hoechst Ag | 3,4-dihydroxypyrrolidin-2-on-derivate, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung sowie die bei der herstellung anfallenden neuen zwischenprodukte |
| EP0407701A3 (en) * | 1989-05-15 | 1992-04-22 | Fujisawa Pharmaceutical Co., Ltd. | Antiretroviral pyrroline and pyrrolidine sulfonic acid derivatives |
| EP2164325B1 (en) | 2007-05-31 | 2013-04-24 | Shionogi&Co., Ltd. | Oxyimino compounds and the use thereof |
| ES2408159T3 (es) * | 2008-06-11 | 2013-06-18 | Shionogi & Co., Ltd. | Compuestos de oxicarbamoilo y su utilización |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1000308A (fr) * | 1949-05-28 | 1952-02-11 | Basf Ag | Procédé pour la production de 3. 4-dioxypyrrolidines |
| FR1000310A (fr) * | 1949-06-18 | 1952-02-11 | Basf Ag | Procédé pour la production de dérivés de pyrrolidine |
| FR1532221A (fr) * | 1963-10-22 | 1968-07-12 | Robins Co Inc A H | Procédé de production de n, n-di (aryl monocarbocyclique)-carbamates de 1-(alkylinférieur)-3-pyrrolidyle |
| CH521338A (de) * | 1967-03-13 | 1972-04-15 | Robins Co Inc A H | Verfahren zur Herstellung von neuen Pyrrolidinderivaten |
| US3577415A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-substituted phenoxypyrrolidines |
| IE45511B1 (en) * | 1976-09-01 | 1982-09-08 | Ciba Geigy Ag | New derivatives of perhydro-aza-heterocycles and processesfor the production thereof |
-
1980
- 1980-01-03 MX MX808576U patent/MX6634E/es unknown
- 1980-01-07 SE SE8000085A patent/SE435927B/sv not_active IP Right Cessation
- 1980-01-08 IT IT67020/80A patent/IT1127967B/it active
- 1980-01-08 FR FR8000272A patent/FR2446279B1/fr not_active Expired
- 1980-01-08 CH CH10280A patent/CH643243A5/fr not_active IP Right Cessation
- 1980-01-09 JP JP123280A patent/JPS5598160A/ja active Granted
- 1980-01-09 GB GB8000709A patent/GB2040933B/en not_active Expired
- 1980-01-09 DE DE19803000625 patent/DE3000625A1/de active Granted
- 1980-01-09 CA CA343,328A patent/CA1133495A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2040933B (en) | 1983-07-20 |
| CH643243A5 (fr) | 1984-05-30 |
| JPS648621B2 (en]) | 1989-02-14 |
| SE435927B (sv) | 1984-10-29 |
| FR2446279A1 (fr) | 1980-08-08 |
| DE3000625C2 (en]) | 1989-04-20 |
| FR2446279B1 (fr) | 1985-10-31 |
| SE8000085L (sv) | 1980-08-26 |
| IT8067020A0 (it) | 1980-01-08 |
| JPS5598160A (en) | 1980-07-25 |
| IT1127967B (it) | 1986-05-28 |
| DE3000625A1 (de) | 1980-07-17 |
| MX6634E (es) | 1985-09-12 |
| GB2040933A (en) | 1980-09-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |