DE3103080A1 - "spiro (dihydrobenzofuran-piperidine und -pyrrolidine)" - Google Patents
"spiro (dihydrobenzofuran-piperidine und -pyrrolidine)"Info
- Publication number
- DE3103080A1 DE3103080A1 DE19813103080 DE3103080A DE3103080A1 DE 3103080 A1 DE3103080 A1 DE 3103080A1 DE 19813103080 DE19813103080 DE 19813103080 DE 3103080 A DE3103080 A DE 3103080A DE 3103080 A1 DE3103080 A1 DE 3103080A1
- Authority
- DE
- Germany
- Prior art keywords
- pyrryl
- dihydro
- spiro
- benzofuran
- piperidine
- 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.)
- Withdrawn
Links
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 10
- -1 phenoxyearbonyl Chemical group 0.000 claims description 79
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 150000001875 compounds Chemical class 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 230000000269 nucleophilic effect Effects 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 4
- YZKAGUHQYDCQOL-UHFFFAOYSA-N 2-benzyl-1h-pyrrole Chemical class C=1C=CC=CC=1CC1=CC=CN1 YZKAGUHQYDCQOL-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 47
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 229910052799 carbon Inorganic materials 0.000 description 34
- 239000000203 mixture Substances 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000002904 solvent Substances 0.000 description 31
- 125000003003 spiro group Chemical group 0.000 description 31
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000003921 oil Substances 0.000 description 27
- 235000019198 oils Nutrition 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 238000010992 reflux Methods 0.000 description 22
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 125000002252 acyl group Chemical group 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 150000003891 oxalate salts Chemical class 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 5
- ZELCJNKQCKIECO-UHFFFAOYSA-N spiro[3h-1-benzofuran-2,4'-piperidine] Chemical compound C1C2=CC=CC=C2OC11CCNCC1 ZELCJNKQCKIECO-UHFFFAOYSA-N 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- SWOUKRUCSQVIAI-UHFFFAOYSA-N 3-pyrrol-1-ylspiro[3h-1-benzofuran-2,4'-piperidine] Chemical compound C1CNCCC21C(N1C=CC=C1)C1=CC=CC=C1O2 SWOUKRUCSQVIAI-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- LFSHYTUSNOERFO-UHFFFAOYSA-N 1-benzofuran;piperidine Chemical compound C1CCNCC1.C1=CC=C2OC=CC2=C1 LFSHYTUSNOERFO-UHFFFAOYSA-N 0.000 description 3
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 150000003235 pyrrolidines Chemical class 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- ZUAMGAODWYGAHS-UHFFFAOYSA-N 1'-methyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,4'-piperidine] Chemical compound C1CN(C)CCC21C(N1C=CC=C1)C1=CC=CC=C1O2 ZUAMGAODWYGAHS-UHFFFAOYSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- GPSDCMUQBLNIJM-UHFFFAOYSA-N 3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine] Chemical compound C1CCNCC21C(N1C=CC=C1)C1=CC=CC=C1O2 GPSDCMUQBLNIJM-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- CMHJINRPYOPNBL-UHFFFAOYSA-N phenyl 3-pyrrol-1-ylspiro[3h-1-benzofuran-2,4'-piperidine]-1'-carboxylate Chemical compound C1CC2(C(C3=CC=CC=C3O2)N2C=CC=C2)CCN1C(=O)OC1=CC=CC=C1 CMHJINRPYOPNBL-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- GASOCDUVJSYZGK-UHFFFAOYSA-N spirobenzofuran Chemical compound C1=2C=C(O)C(C)=CC=2OC(O)C21CC(=O)CC2(C)C GASOCDUVJSYZGK-UHFFFAOYSA-N 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XWAZFBAFYTWHCP-UHFFFAOYSA-N 1'-(2-phenylethyl)-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine] Chemical compound C1CCC2(C(C3=CC=CC=C3O2)N2C=CC=C2)CN1CCC1=CC=CC=C1 XWAZFBAFYTWHCP-UHFFFAOYSA-N 0.000 description 1
- CGADIWFQMQRLCQ-UHFFFAOYSA-N 1'-hexyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine] Chemical compound C1N(CCCCCC)CCC21C(N1C=CC=C1)C1=CC=CC=C1O2 CGADIWFQMQRLCQ-UHFFFAOYSA-N 0.000 description 1
- SSJMFHFVVVHPMD-UHFFFAOYSA-N 1'-methyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine] Chemical compound C1N(C)CCCC21C(N1C=CC=C1)C1=CC=CC=C1O2 SSJMFHFVVVHPMD-UHFFFAOYSA-N 0.000 description 1
- WMBAOQGKEFYPIH-UHFFFAOYSA-N 1'-methyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine] Chemical compound C1N(C)CCC21C(N1C=CC=C1)C1=CC=CC=C1O2 WMBAOQGKEFYPIH-UHFFFAOYSA-N 0.000 description 1
- WZZDLFVFDHZWOL-UHFFFAOYSA-N 1'-propyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine] Chemical compound C1N(CCC)CCCC21C(N1C=CC=C1)C1=CC=CC=C1O2 WZZDLFVFDHZWOL-UHFFFAOYSA-N 0.000 description 1
- ILJNYCQVMQGQPA-UHFFFAOYSA-N 1-(3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine]-1'-yl)ethanone Chemical compound C1N(C(=O)C)CCCC21C(N1C=CC=C1)C1=CC=CC=C1O2 ILJNYCQVMQGQPA-UHFFFAOYSA-N 0.000 description 1
- HYOJANGOMPESLP-UHFFFAOYSA-N 1-(3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine]-1'-yl)butan-1-one Chemical compound C1N(C(=O)CCC)CCC21C(N1C=CC=C1)C1=CC=CC=C1O2 HYOJANGOMPESLP-UHFFFAOYSA-N 0.000 description 1
- LVIJVENECGXMIX-UHFFFAOYSA-N 1-(5-bromo-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine]-1'-yl)ethanone Chemical compound C1N(C(=O)C)CCC21C(N1C=CC=C1)C1=CC(Br)=CC=C1O2 LVIJVENECGXMIX-UHFFFAOYSA-N 0.000 description 1
- YRWSRHFXUVTMNV-UHFFFAOYSA-N 1-(5-fluoro-3-pyrrol-1-ylspiro[3H-1-benzofuran-2,3'-piperidine]-1'-yl)pentan-1-one Chemical compound C1N(C(=O)CCCC)CCCC21C(N1C=CC=C1)C1=CC(F)=CC=C1O2 YRWSRHFXUVTMNV-UHFFFAOYSA-N 0.000 description 1
- DRCFPUPCLGWXAJ-UHFFFAOYSA-N 1-(5-methyl-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine]-1'-yl)ethanone Chemical compound C1N(C(=O)C)CCC21C(N1C=CC=C1)C1=CC(C)=CC=C1O2 DRCFPUPCLGWXAJ-UHFFFAOYSA-N 0.000 description 1
- BMEWLJMRNCDJMS-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]pyrrole Chemical compound FC1=CC=CC=C1CN1C=CC=C1 BMEWLJMRNCDJMS-UHFFFAOYSA-N 0.000 description 1
- DHGMDHQNUNRMIN-UHFFFAOYSA-N 1-benzylpyrrolidin-3-one Chemical compound C1C(=O)CCN1CC1=CC=CC=C1 DHGMDHQNUNRMIN-UHFFFAOYSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical compound ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 1
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 1
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 1
- YMDNODNLFSHHCV-UHFFFAOYSA-N 2-chloro-n,n-diethylethanamine Chemical compound CCN(CC)CCCl YMDNODNLFSHHCV-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
- FGNJSPYXRKKMMB-UHFFFAOYSA-N 3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine]-1'-carbonitrile Chemical compound C1N(C#N)CCCC21C(N1C=CC=C1)C1=CC=CC=C1O2 FGNJSPYXRKKMMB-UHFFFAOYSA-N 0.000 description 1
- WMOCBGCJCIMTPB-UHFFFAOYSA-N 4-(5-bromo-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine]-1'-yl)-2-methyl-1-phenylbutan-1-one Chemical compound C=1C=CC=CC=1C(=O)C(C)CCN(C1)CCC21OC1=CC=C(Br)C=C1C2N1C=CC=C1 WMOCBGCJCIMTPB-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- PNUCCPFHVYOGSD-UHFFFAOYSA-N 5-bromo-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-pyrrolidine] Chemical compound C1=CC=CN1C1C2=CC(Br)=CC=C2OC21CCNC2 PNUCCPFHVYOGSD-UHFFFAOYSA-N 0.000 description 1
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- ZXIMFATVTCRKIM-UHFFFAOYSA-N oxalic acid 1'-(2-phenylethyl)-3-pyrrol-1-ylspiro[3H-1-benzofuran-2,4'-piperidine] Chemical compound OC(=O)C(O)=O.C1CC2(C(C3=CC=CC=C3O2)N2C=CC=C2)CCN1CCC1=CC=CC=C1 ZXIMFATVTCRKIM-UHFFFAOYSA-N 0.000 description 1
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- AIAWROISJJXPKH-UHFFFAOYSA-N phenyl 5-bromo-3-pyrrol-1-ylspiro[3H-1-benzofuran-2,3'-pyrrolidine]-1'-carboxylate Chemical compound C1=CC=CN1C1C2=CC(Br)=CC=C2OC1(C1)CCN1C(=O)OC1=CC=CC=C1 AIAWROISJJXPKH-UHFFFAOYSA-N 0.000 description 1
- BHHZVFVJJWMRRQ-UHFFFAOYSA-N phenyl 5-chloro-3-pyrrol-1-ylspiro[3h-1-benzofuran-2,3'-piperidine]-1'-carboxylate Chemical compound C1=CC=CN1C1C2=CC(Cl)=CC=C2OC1(C1)CCCN1C(=O)OC1=CC=CC=C1 BHHZVFVJJWMRRQ-UHFFFAOYSA-N 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
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- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical class O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
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- 238000001953 recrystallisation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- NWVKCARSJJXIPN-UHFFFAOYSA-N spiro[3h-1-benzofuran-2,3'-piperidine] Chemical compound C1C2=CC=CC=C2OC11CCCNC1 NWVKCARSJJXIPN-UHFFFAOYSA-N 0.000 description 1
- GUHDZSDMRIYDIV-UHFFFAOYSA-N spiro[3h-1-benzofuran-2,3'-pyrrolidine] Chemical compound C1NCCC21OC1=CC=CC=C1C2 GUHDZSDMRIYDIV-UHFFFAOYSA-N 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- 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
- C07D491/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/118,146 US4268515A (en) | 1980-02-04 | 1980-02-04 | Spiro[dihydrobenzofuran-piperidines and-pyrrolidines], pharmaceutical compositions thereof and methods of use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3103080A1 true DE3103080A1 (de) | 1981-12-17 |
Family
ID=22376742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19813103080 Withdrawn DE3103080A1 (de) | 1980-02-04 | 1981-01-30 | "spiro (dihydrobenzofuran-piperidine und -pyrrolidine)" |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4268515A (enExample) |
| JP (1) | JPS56125389A (enExample) |
| DE (1) | DE3103080A1 (enExample) |
| FR (1) | FR2477153A1 (enExample) |
| GB (1) | GB2068951B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4329464A (en) * | 1981-05-20 | 1982-05-11 | Hoechst-Roussel Pharmaceuticals Inc. | Spiro[dihydrobenzofuran-piperidines and -pyrrolidines] |
| US4918069A (en) * | 1987-07-30 | 1990-04-17 | Hoechst-Roussel Pharmaceuticals Inc. | Spiro[(piperidine- pyrrolidine- or hexahydroazepinyl substituted) pyrrolo[2,][1,4]benzoxazepines] |
| US4812450A (en) * | 1987-07-30 | 1989-03-14 | Hoechst-Roussel Pharmaceuticals Inc. | Spiro((piperidine-pyrrolidine- or hexahydroazepinyl substituted) pyrrolo(2,1-C) (1,4)benzoxazepines) |
| US5215984A (en) * | 1987-07-30 | 1993-06-01 | Hoechst-Roussel Pharmaceuticals Inc. | Antihypertensive spiro(piperidine- pyrrolidine- or hexahydroazepinyl substituted) pyrrolo(2,1-c)(1,4)benzoxazepines) |
| JP3882224B2 (ja) * | 1996-05-31 | 2007-02-14 | 旭硝子株式会社 | パロキセチンの製造方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3686186A (en) * | 1970-10-05 | 1972-08-22 | William J Houlihan | Substituted isochroman or phthalan piperidenes |
| US3959475A (en) * | 1973-12-12 | 1976-05-25 | American Hoechst Corporation | Substituted 1,3-dihydrospiro(isobenzofuran)s |
| US3962259A (en) * | 1973-12-12 | 1976-06-08 | American Hoechst Corporation | 1,3-Dihydrospiro[isobenzofuran]s and derivatives thereof |
| US4024263A (en) * | 1975-04-30 | 1977-05-17 | American Hoechst Corporation | 1,3-Dihydrospiro[isobenzofuran-1,4'-piperidine]s |
| US4166119A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines |
| US4166120A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing benzoylpropyl-spiro[dihydrobenzofuran]piperidines and pyrrolidines |
-
1980
- 1980-02-04 US US06/118,146 patent/US4268515A/en not_active Expired - Lifetime
-
1981
- 1981-01-30 DE DE19813103080 patent/DE3103080A1/de not_active Withdrawn
- 1981-02-04 GB GB8103392A patent/GB2068951B/en not_active Expired
- 1981-02-04 JP JP1627781A patent/JPS56125389A/ja active Pending
- 1981-02-04 FR FR8102106A patent/FR2477153A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS56125389A (en) | 1981-10-01 |
| GB2068951B (en) | 1984-10-03 |
| GB2068951A (en) | 1981-08-19 |
| FR2477153B1 (enExample) | 1983-12-16 |
| US4268515A (en) | 1981-05-19 |
| FR2477153A1 (fr) | 1981-09-04 |
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