CH556837A - Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. - Google Patents
Verfahren zur herstellung neuer spiroindanpyrrolidinderivate.Info
- Publication number
- CH556837A CH556837A CH1827473A CH1827473A CH556837A CH 556837 A CH556837 A CH 556837A CH 1827473 A CH1827473 A CH 1827473A CH 1827473 A CH1827473 A CH 1827473A CH 556837 A CH556837 A CH 556837A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compounds
- indan
- group
- acid
- Prior art date
Links
- 229940035676 analgesics Drugs 0.000 title 1
- 239000000730 antalgic agent Substances 0.000 title 1
- 229940125723 sedative agent Drugs 0.000 title 1
- 239000000932 sedative agent Substances 0.000 title 1
- -1 methylenedioxy Chemical group 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 150000003235 pyrrolidines Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 239000000463 material Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- VZCYOOQTPOCHFL-OWOJBTEDSA-M fumarate(1-) Chemical compound OC(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-M 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UHKAJLSKXBADFT-UHFFFAOYSA-N 1,3-indandione Chemical compound C1=CC=C2C(=O)CC(=O)C2=C1 UHKAJLSKXBADFT-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KXZFLCZIUFIXAU-UHFFFAOYSA-N 6-methylspiro[1,2-dihydroindene-3,3'-pyrrolidine]-1-ol Chemical compound C=1C(C)=CC=C2C=1C(O)CC21CCNC1 KXZFLCZIUFIXAU-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000013016 damping Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- SPFLXYFHASMZPS-UHFFFAOYSA-N 6-chlorospiro[1,2-dihydroindene-3,3'-pyrrolidine]-1-ol Chemical compound C12=CC=C(Cl)C=C2C(O)CC21CCNC2 SPFLXYFHASMZPS-UHFFFAOYSA-N 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- VUWPIBNKJSEYIN-UHFFFAOYSA-N diethyl 2-benzylidenepropanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CC1=CC=CC=C1 VUWPIBNKJSEYIN-UHFFFAOYSA-N 0.000 description 2
- VFIQYNCJSDGNGB-UHFFFAOYSA-N diethyl 3-cyano-3-phenylpentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)(C#N)C1=CC=CC=C1 VFIQYNCJSDGNGB-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- KZPNXPYMYHZEHR-UHFFFAOYSA-N spiro[1,2-dihydroindene-3,3'-pyrrolidine]-1-ol Chemical compound C12=CC=CC=C2C(O)CC21CCNC2 KZPNXPYMYHZEHR-UHFFFAOYSA-N 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- ZWHAYRITAMAMDO-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(1-hydroxy-6-methylspiro[1,2-dihydroindene-3,3'-pyrrolidine]-1'-yl)butan-1-one Chemical compound C=1C(C)=CC=C2C=1C(O)CC2(C1)CCN1CCCC(=O)C1=CC=C(F)C=C1 ZWHAYRITAMAMDO-UHFFFAOYSA-N 0.000 description 1
- TUGATRAPWYKNCO-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(1-hydroxyspiro[1,2-dihydroindene-3,3'-pyrrolidine]-1'-yl)butan-1-one Chemical class C12=CC=CC=C2C(O)CC1(C1)CCN1CCCC(=O)C1=CC=C(F)C=C1 TUGATRAPWYKNCO-UHFFFAOYSA-N 0.000 description 1
- PKEZERYCBVTLKR-UHFFFAOYSA-N 1-hydroxyspiro[1,2-dihydroindene-3,4'-pyrrolidine]-2'-one Chemical compound C12=CC=CC=C2C(O)CC21CNC(=O)C2 PKEZERYCBVTLKR-UHFFFAOYSA-N 0.000 description 1
- DYPHDCYZFREKGF-UHFFFAOYSA-N 2-[3-(4-chlorophenyl)-5-oxopyrrolidin-3-yl]acetic acid Chemical compound C=1C=C(Cl)C=CC=1C1(CC(=O)O)CNC(=O)C1 DYPHDCYZFREKGF-UHFFFAOYSA-N 0.000 description 1
- SSVWUMNZROSQRI-UHFFFAOYSA-N 2-ethoxycarbonyl-3-(4-methylphenyl)prop-2-enoic acid Chemical compound CCOC(=O)C(C(O)=O)=CC1=CC=C(C)C=C1 SSVWUMNZROSQRI-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
- HXAOUYGZEOZTJO-UHFFFAOYSA-N 4-chloro-1-(4-fluorophenyl)butan-1-one Chemical compound FC1=CC=C(C(=O)CCCCl)C=C1 HXAOUYGZEOZTJO-UHFFFAOYSA-N 0.000 description 1
- YBCJZEBAZYSAQY-UHFFFAOYSA-N 6-chloro-1-hydroxyspiro[1,2-dihydroindene-3,4'-pyrrolidine]-2'-one Chemical compound C12=CC=C(Cl)C=C2C(O)CC21CNC(=O)C2 YBCJZEBAZYSAQY-UHFFFAOYSA-N 0.000 description 1
- QTWDHUCWZJYKJN-UHFFFAOYSA-N 6-chlorospiro[2h-indene-3,4'-pyrrolidine]-1,2'-dione Chemical compound C=1C(Cl)=CC=C2C=1C(=O)CC21CNC(=O)C1 QTWDHUCWZJYKJN-UHFFFAOYSA-N 0.000 description 1
- TWZQXGRKDWKGII-UHFFFAOYSA-N 6-methylspiro[1,2-dihydroindene-3,3'-pyrrolidine] Chemical compound C=1C(C)=CC=C2C=1CCC21CCNC1 TWZQXGRKDWKGII-UHFFFAOYSA-N 0.000 description 1
- RQMSEXVSNRWDMM-UHFFFAOYSA-N 6-methylspiro[2h-indene-3,4'-pyrrolidine]-1,2'-dione Chemical compound C=1C(C)=CC=C2C=1C(=O)CC21CNC(=O)C1 RQMSEXVSNRWDMM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- YTWFRDISFWCLRK-UHFFFAOYSA-N [1'-[4-(4-fluorophenyl)-4-oxobutyl]-6-methylspiro[1,2-dihydroindene-3,3'-pyrrolidine]-1-yl] propanoate Chemical compound C12=CC=C(C)C=C2C(OC(=O)CC)CC1(C1)CCN1CCCC(=O)C1=CC=C(F)C=C1 YTWFRDISFWCLRK-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- MVRRBDRVDOIABW-UHFFFAOYSA-N diethyl 2-[(4-chlorophenyl)methylidene]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CC1=CC=C(Cl)C=C1 MVRRBDRVDOIABW-UHFFFAOYSA-N 0.000 description 1
- NRJURUPAVGNABO-UHFFFAOYSA-N diethyl 3-(4-chlorophenyl)-3-cyanopentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)(C#N)C1=CC=C(Cl)C=C1 NRJURUPAVGNABO-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- SYKQOFCBFHMCJV-UHFFFAOYSA-N ethyl 2-cyano-3-phenylpropanoate Chemical compound CCOC(=O)C(C#N)CC1=CC=CC=C1 SYKQOFCBFHMCJV-UHFFFAOYSA-N 0.000 description 1
- XEZYVIMQKOFWRH-UHFFFAOYSA-N ethyl 3-(4-chlorophenyl)-3-cyanopropanoate Chemical compound CCOC(=O)CC(C#N)C1=CC=C(Cl)C=C1 XEZYVIMQKOFWRH-UHFFFAOYSA-N 0.000 description 1
- HJKJXWMIISKYGB-UHFFFAOYSA-N ethyl 3-cyano-3-phenylpropanoate Chemical compound CCOC(=O)CC(C#N)C1=CC=CC=C1 HJKJXWMIISKYGB-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UKFXDFUAPNAMPJ-UHFFFAOYSA-N ethylmalonic acid Chemical compound CCC(C(O)=O)C(O)=O UKFXDFUAPNAMPJ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- ISMJKHRIUPIVGK-UHFFFAOYSA-N spiro[2h-indene-3,4'-pyrrolidine]-1,2'-dione Chemical compound C1NC(=O)CC21C1=CC=CC=C1C(=O)C2 ISMJKHRIUPIVGK-UHFFFAOYSA-N 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/96—Spiro-condensed ring systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1827473A CH556837A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1827473A CH556837A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
| CH1231871A CH556835A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH556837A true CH556837A (de) | 1974-12-13 |
Family
ID=4381893
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1827473A CH556837A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
| CH1231871A CH556835A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1231871A CH556835A (de) | 1971-08-23 | 1971-08-23 | Verfahren zur herstellung neuer spiroindanpyrrolidinderivate. |
Country Status (16)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7312262A (enrdf_load_stackoverflow) * | 1972-09-11 | 1974-03-13 | ||
| FR2207718A2 (en) * | 1972-11-28 | 1974-06-21 | Sandoz Sa | Analgesic and sedative spiro (indane 1:3'-pyrrolidines) - 4-(spiro (5-substd.-3-hydroxy or acyloxy-indane-1:3'-pyrrolidine)-1'-yl)-p-fluorobutyrophene derivs |
| JPS5933344A (ja) * | 1982-08-19 | 1984-02-23 | Mitsubishi Monsanto Chem Co | 塩化ビニル系樹脂組成物 |
| US5948807A (en) * | 1997-09-03 | 1999-09-07 | Regents Of The University Of Minnesota | Spiroindanamines and Spiroindanimides |
| EP1420781A2 (en) * | 2001-08-29 | 2004-05-26 | Endo Pharmaceuticals Inc. | Analgetic pyrroline derivatives |
| EP3233799B1 (en) | 2014-12-19 | 2021-05-19 | The Broad Institute, Inc. | Dopamine d2 receptor ligands |
| WO2016100940A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute, Inc. | Dopamine d2 receptor ligands |
-
0
- BE BE787804D patent/BE787804A/xx unknown
-
1971
- 1971-08-23 CH CH1827473A patent/CH556837A/de not_active IP Right Cessation
- 1971-08-23 CH CH1231871A patent/CH556835A/xx not_active IP Right Cessation
-
1972
- 1972-04-21 ES ES406008A patent/ES406008A1/es not_active Expired
- 1972-08-14 SE SE7210502A patent/SE385584B/xx unknown
- 1972-08-18 NL NL7211304A patent/NL7211304A/xx unknown
- 1972-08-18 FR FR7229540A patent/FR2150797B1/fr not_active Expired
- 1972-08-21 GB GB451775A patent/GB1401049A/en not_active Expired
- 1972-08-21 PL PL1972157376A patent/PL79446B1/pl unknown
- 1972-08-21 GB GB3880272A patent/GB1401048A/en not_active Expired
- 1972-08-21 DE DE2241027A patent/DE2241027A1/de active Pending
- 1972-08-22 HU HUSA2388A patent/HU165127B/hu unknown
- 1972-08-22 IL IL40177A patent/IL40177A0/xx unknown
- 1972-08-22 AT AT722872A patent/AT330167B/de not_active IP Right Cessation
- 1972-08-22 JP JP47084027A patent/JPS4829765A/ja active Pending
- 1972-08-23 AU AU45897/72A patent/AU4589772A/en not_active Expired
- 1972-08-23 DD DD165200A patent/DD102146A5/xx unknown
- 1972-08-23 ZA ZA740329*DA patent/ZA74329B/xx unknown
- 1972-08-23 ZA ZA725796A patent/ZA725796B/xx unknown
-
1974
- 1974-07-24 AT AT607274A patent/ATA607274A/de not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL40177A0 (en) | 1972-10-29 |
| BE787804A (fr) | 1973-02-21 |
| ZA74329B (en) | 1974-05-29 |
| DD102146A5 (enrdf_load_stackoverflow) | 1973-12-05 |
| ATA722872A (de) | 1975-09-15 |
| PL79446B1 (en) | 1975-06-30 |
| AT330167B (de) | 1976-06-25 |
| DE2241027A1 (de) | 1973-03-01 |
| HU165127B (enrdf_load_stackoverflow) | 1974-06-28 |
| FR2150797A1 (enrdf_load_stackoverflow) | 1973-04-13 |
| SE385584B (sv) | 1976-07-12 |
| ZA725796B (en) | 1974-04-24 |
| FR2150797B1 (enrdf_load_stackoverflow) | 1976-04-16 |
| AU4589772A (en) | 1974-02-28 |
| CH556835A (de) | 1974-12-13 |
| ATA607274A (de) | 1975-09-15 |
| NL7211304A (enrdf_load_stackoverflow) | 1973-02-27 |
| ES406008A1 (es) | 1976-06-01 |
| JPS4829765A (enrdf_load_stackoverflow) | 1973-04-19 |
| GB1401049A (en) | 1975-07-16 |
| GB1401048A (en) | 1975-07-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |