CA1191857A - 3,3-dialkyl- and 3,3-alkylene-indoline derivatives, and processes for their production - Google Patents
3,3-dialkyl- and 3,3-alkylene-indoline derivatives, and processes for their productionInfo
- Publication number
- CA1191857A CA1191857A CA000419841A CA419841A CA1191857A CA 1191857 A CA1191857 A CA 1191857A CA 000419841 A CA000419841 A CA 000419841A CA 419841 A CA419841 A CA 419841A CA 1191857 A CA1191857 A CA 1191857A
- Authority
- CA
- Canada
- Prior art keywords
- indoline
- formula
- hydroxy
- 6alkoxy
- hydrolysable
- 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
- 238000000034 method Methods 0.000 title claims description 28
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000002253 acid Substances 0.000 claims abstract description 32
- 150000002148 esters Chemical class 0.000 claims abstract description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 25
- 239000012458 free base Substances 0.000 claims description 16
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 238000005661 deetherification reaction Methods 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- 150000002476 indolines Chemical class 0.000 abstract description 19
- 230000000202 analgesic effect Effects 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 41
- 235000013350 formula milk Nutrition 0.000 description 41
- 239000000047 product Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000007858 starting material Substances 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 20
- 238000007792 addition Methods 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 229940035423 ethyl ether Drugs 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 230000010933 acylation Effects 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000010555 transalkylation reaction Methods 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
- -1 hydroxy, methoxy Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 3
- 229940093499 ethyl acetate Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- CNYMFJWCSOZAFV-UHFFFAOYSA-N 3,3-dimethyl-5-propan-2-yloxy-1,2-dihydroindole Chemical compound CC(C)OC1=CC=C2NCC(C)(C)C2=C1 CNYMFJWCSOZAFV-UHFFFAOYSA-N 0.000 description 2
- AYVGKVADTZHDDD-UHFFFAOYSA-N 5-ethoxy-3,3-dimethyl-1,2-dihydroindole Chemical compound CCOC1=CC=C2NCC(C)(C)C2=C1 AYVGKVADTZHDDD-UHFFFAOYSA-N 0.000 description 2
- JYWXNYIUDFMBCL-UHFFFAOYSA-N 5-methoxy-3,3-dimethyl-1,2-dihydroindole Chemical compound COC1=CC=C2NCC(C)(C)C2=C1 JYWXNYIUDFMBCL-UHFFFAOYSA-N 0.000 description 2
- ZOJZYAPVVOLQQB-UHFFFAOYSA-N 6-hydroxy-1,3-dihydroindol-2-one Chemical compound OC1=CC=C2CC(=O)NC2=C1 ZOJZYAPVVOLQQB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910015148 B2H6 Inorganic materials 0.000 description 2
- 229910015845 BBr3 Inorganic materials 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- QKRCABDPWBSLJB-UHFFFAOYSA-N 1-(5-ethoxy-3,3-dimethyl-2h-indol-1-yl)ethanone Chemical compound CCOC1=CC=C2N(C(C)=O)CC(C)(C)C2=C1 QKRCABDPWBSLJB-UHFFFAOYSA-N 0.000 description 1
- YQWYYXJNNSNDIA-UHFFFAOYSA-N 3,3-dimethyl-1,2-dihydroindol-6-ol Chemical compound OC1=CC=C2C(C)(C)CNC2=C1 YQWYYXJNNSNDIA-UHFFFAOYSA-N 0.000 description 1
- OCEMCBBMNJBAJI-UHFFFAOYSA-N 4-ethoxy-3,3-dimethyl-1,2-dihydroindole Chemical compound CCOC1=CC=CC2=C1C(C)(C)CN2 OCEMCBBMNJBAJI-UHFFFAOYSA-N 0.000 description 1
- FTJQLPXJRKHATE-UHFFFAOYSA-N 4-hydroxy-1,3-dihydroindol-2-one Chemical compound OC1=CC=CC2=C1CC(=O)N2 FTJQLPXJRKHATE-UHFFFAOYSA-N 0.000 description 1
- DYTNNGQPYKZMNF-UHFFFAOYSA-N 5-ethoxy-1,3-dihydroindol-2-one Chemical compound CCOC1=CC=C2NC(=O)CC2=C1 DYTNNGQPYKZMNF-UHFFFAOYSA-N 0.000 description 1
- DLQFYVZWDIHNKX-UHFFFAOYSA-N 5-ethoxy-3,3,7-trimethyl-1,2-dihydroindole Chemical compound CC1=CC(OCC)=CC2=C1NCC2(C)C DLQFYVZWDIHNKX-UHFFFAOYSA-N 0.000 description 1
- MCACNMMKZCKXAT-UHFFFAOYSA-N 5-ethoxy-3,3,7-trimethyl-1h-indol-2-one Chemical compound CC1=CC(OCC)=CC2=C1NC(=O)C2(C)C MCACNMMKZCKXAT-UHFFFAOYSA-N 0.000 description 1
- IVMYKLYNZCWHTC-UHFFFAOYSA-N 5-hydroxy-3,3-dimethyl-1h-indol-2-one Chemical compound C1=C(O)C=C2C(C)(C)C(=O)NC2=C1 IVMYKLYNZCWHTC-UHFFFAOYSA-N 0.000 description 1
- DFGZEOUBIHLXFD-UHFFFAOYSA-N 5-methoxy-1,3-dihydroindol-2-one Chemical compound COC1=CC=C2NC(=O)CC2=C1 DFGZEOUBIHLXFD-UHFFFAOYSA-N 0.000 description 1
- IGRJLJWPPSJVTG-UHFFFAOYSA-N 5-methoxy-1,3-dimethyl-2-nitrobenzene Chemical compound COC1=CC(C)=C([N+]([O-])=O)C(C)=C1 IGRJLJWPPSJVTG-UHFFFAOYSA-N 0.000 description 1
- KKXRYAPPQOIPCX-UHFFFAOYSA-N 5-methoxy-3,3,7-trimethyl-1,2-dihydroindole Chemical compound CC1=CC(OC)=CC2=C1NCC2(C)C KKXRYAPPQOIPCX-UHFFFAOYSA-N 0.000 description 1
- ZCKUVSBCERFEKZ-UHFFFAOYSA-N 5-methoxy-7-methyl-1,3-dihydroindol-2-one Chemical compound CC1=CC(OC)=CC2=C1NC(=O)C2 ZCKUVSBCERFEKZ-UHFFFAOYSA-N 0.000 description 1
- HRINDOHVNYBEQJ-UHFFFAOYSA-N 5-propan-2-yloxy-1,3-dihydroindol-2-one Chemical compound CC(C)OC1=CC=C2NC(=O)CC2=C1 HRINDOHVNYBEQJ-UHFFFAOYSA-N 0.000 description 1
- LTQXKFWKDLQHPY-UHFFFAOYSA-N 6-ethoxy-3,3,5-trimethyl-1h-indol-2-one Chemical compound C1=C(C)C(OCC)=CC2=C1C(C)(C)C(=O)N2 LTQXKFWKDLQHPY-UHFFFAOYSA-N 0.000 description 1
- ITLRQEKXUKZTPG-UHFFFAOYSA-N 6-ethoxy-3,3-dimethyl-1,2-dihydroindole Chemical compound CCOC1=CC=C2C(C)(C)CNC2=C1 ITLRQEKXUKZTPG-UHFFFAOYSA-N 0.000 description 1
- HYVHHZQCEOYGLL-UHFFFAOYSA-N 7-ethoxy-3,3-dimethyl-1,2-dihydroindole Chemical compound CCOC1=CC=CC2=C1NCC2(C)C HYVHHZQCEOYGLL-UHFFFAOYSA-N 0.000 description 1
- KKIHSFZXMUNNIG-UHFFFAOYSA-N 7-ethoxy-3,3-dimethyl-1h-indol-2-one Chemical compound CCOC1=CC=CC2=C1NC(=O)C2(C)C KKIHSFZXMUNNIG-UHFFFAOYSA-N 0.000 description 1
- OAHKNTGVVFWRJJ-UHFFFAOYSA-N 7-hydroxy-3,3-dimethyl-1h-indol-2-one Chemical compound C1=CC=C(O)C2=C1C(C)(C)C(=O)N2 OAHKNTGVVFWRJJ-UHFFFAOYSA-N 0.000 description 1
- BHIXTFSJENSHBP-UHFFFAOYSA-N 7-methoxy-3,3-dimethyl-1h-indol-2-one Chemical compound COC1=CC=CC2=C1NC(=O)C2(C)C BHIXTFSJENSHBP-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 241001136792 Alle Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000036366 Sensation of pressure 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
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000000332 continued effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 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
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005924 transacylation reaction Methods 0.000 description 1
Classifications
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH37382 | 1982-01-21 | ||
| CH373/82 | 1982-01-21 | ||
| CH374582 | 1982-06-17 | ||
| CH3745/82 | 1982-06-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1191857A true CA1191857A (en) | 1985-08-13 |
Family
ID=25684383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000419841A Expired CA1191857A (en) | 1982-01-21 | 1983-01-20 | 3,3-dialkyl- and 3,3-alkylene-indoline derivatives, and processes for their production |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US4622336A (en, 2012) |
| AT (1) | AT381490B (en, 2012) |
| AU (1) | AU565538B2 (en, 2012) |
| CA (1) | CA1191857A (en, 2012) |
| CH (1) | CH657848A5 (en, 2012) |
| CY (1) | CY1431A (en, 2012) |
| DE (1) | DE3300522A1 (en, 2012) |
| DK (1) | DK161071C (en, 2012) |
| ES (1) | ES519108A0 (en, 2012) |
| FI (1) | FI79098C (en, 2012) |
| FR (1) | FR2519982B1 (en, 2012) |
| GB (1) | GB2113682B (en, 2012) |
| HK (1) | HK56888A (en, 2012) |
| HU (1) | HU189215B (en, 2012) |
| IE (1) | IE54878B1 (en, 2012) |
| IL (1) | IL67715A (en, 2012) |
| IT (1) | IT1197546B (en, 2012) |
| KE (1) | KE3813A (en, 2012) |
| MY (1) | MY8600467A (en, 2012) |
| NL (1) | NL8300159A (en, 2012) |
| NZ (1) | NZ203056A (en, 2012) |
| PH (1) | PH22848A (en, 2012) |
| PT (1) | PT76110B (en, 2012) |
| SE (1) | SE453293B (en, 2012) |
| SG (1) | SG22688G (en, 2012) |
| WO (1) | WO1983002610A1 (en, 2012) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4690943A (en) * | 1984-09-19 | 1987-09-01 | Pfizer Inc. | Analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds |
| US4803217A (en) * | 1986-12-24 | 1989-02-07 | Merck & Co., Inc. | Hapalindolinone compounds as vassopressin antagonists |
| GB8723157D0 (en) * | 1987-10-02 | 1987-11-04 | Beecham Group Plc | Compounds |
| GB9108965D0 (en) * | 1991-04-26 | 1991-06-12 | Sandoz Ltd | Improvements in or relating to organic compounds |
| FR2708606B1 (fr) * | 1993-07-30 | 1995-10-27 | Sanofi Sa | Dérivés du N-phénylalkylindol-2-one, leur préparation, les compositions pharmaceutiques en contenant. |
| WO2016179157A1 (en) | 2015-05-05 | 2016-11-10 | Carafe Drug Innovation, Llc | Substituted 5-hydroxyoxindoles and their use as analgesics and fever reducers |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE368009B (en, 2012) * | 1971-09-16 | 1974-06-17 | Kabi Ab | |
| AT311332B (de) * | 1971-12-06 | 1973-11-12 | Pierrel Spa | Verfahren zur Herstellung eines neuen Esters von 3,3-Bis(p-hydroxyphenyl)-2-indolinon und dessen Salzen |
| BE524637A (en, 2012) * | 1972-05-17 | |||
| GB1437804A (en) * | 1973-09-10 | 1976-06-03 | Lepetit Spa | Indole derivatives |
| AT346841B (de) * | 1976-11-30 | 1978-11-27 | Delmar Chem | Verfahren zur herstellung von neuen 3- phenylindolinen und ihren salzen |
| FI59246C (fi) * | 1974-06-24 | 1981-07-10 | Otsuka Pharma Co Ltd | Foerfarande foer framstaellning av benscykloamidderivat anvaendbara vid trombos- och emboliterapin |
| JPS597699B2 (ja) * | 1977-02-04 | 1984-02-20 | イハラケミカル工業株式会社 | インドリン類の製造方法 |
| DE2816380A1 (de) * | 1977-04-21 | 1978-12-07 | Hoechst Ag | Spiro eckige klammer auf indolin- 3,4'-piperidine eckige klammer zu und verwandte verbindungen |
| DE2805620A1 (de) * | 1978-02-10 | 1979-08-23 | Basf Ag | Verfahren zur herstellung von indoleninen |
| US4307235A (en) * | 1978-08-23 | 1981-12-22 | American Hoechst Corporation | Spiro[indoline-3,4'-piperidine]s |
| JPS597700B2 (ja) * | 1978-10-31 | 1984-02-20 | イハラケミカル工業株式会社 | インドリン類の製造方法 |
| US4408050A (en) * | 1980-02-15 | 1983-10-04 | American Hoechst Corporation | Spiro(indoline-3,4'-piperidine) and related compounds |
| US4345081A (en) * | 1980-02-15 | 1982-08-17 | American Hoechst Corporation | Spiro[indoline-3,4'-piperidine]s |
| DE3143327A1 (de) * | 1980-11-12 | 1982-06-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "neue indolinone, ihre herstellung und ihre verwendung als arzneimittel" |
| IT1143242B (it) * | 1980-11-18 | 1986-10-22 | Upjohn Co | 1,2,8,ba-ciclopropa(c)-benzo(1,2-b-4,3-b)dipirrol-4(5h)-one antibatte ricamente attivo e relativo metodo di preparazione |
-
1983
- 1983-01-10 DE DE19833300522 patent/DE3300522A1/de active Granted
- 1983-01-12 FR FR8300497A patent/FR2519982B1/fr not_active Expired
- 1983-01-14 FI FI830137A patent/FI79098C/fi not_active IP Right Cessation
- 1983-01-17 NL NL8300159A patent/NL8300159A/nl not_active Application Discontinuation
- 1983-01-19 NZ NZ203056A patent/NZ203056A/en unknown
- 1983-01-19 ES ES519108A patent/ES519108A0/es active Granted
- 1983-01-19 CH CH5162/83A patent/CH657848A5/de not_active IP Right Cessation
- 1983-01-19 PT PT76110A patent/PT76110B/pt not_active IP Right Cessation
- 1983-01-19 IL IL67715A patent/IL67715A/xx not_active IP Right Cessation
- 1983-01-19 AU AU10611/83A patent/AU565538B2/en not_active Ceased
- 1983-01-19 GB GB08301383A patent/GB2113682B/en not_active Expired
- 1983-01-19 DK DK020983A patent/DK161071C/da not_active IP Right Cessation
- 1983-01-19 WO PCT/CH1983/000008 patent/WO1983002610A1/en unknown
- 1983-01-20 HU HU83189A patent/HU189215B/hu not_active IP Right Cessation
- 1983-01-20 IE IE115/83A patent/IE54878B1/en not_active IP Right Cessation
- 1983-01-20 IT IT47588/83A patent/IT1197546B/it active
- 1983-01-20 CA CA000419841A patent/CA1191857A/en not_active Expired
- 1983-01-20 SE SE8300289A patent/SE453293B/sv not_active IP Right Cessation
- 1983-01-20 AT AT0017483A patent/AT381490B/de not_active IP Right Cessation
-
1985
- 1985-01-17 US US06/458,443 patent/US4622336A/en not_active Expired - Fee Related
-
1986
- 1986-01-11 PH PH28376A patent/PH22848A/en unknown
- 1986-12-30 MY MY467/86A patent/MY8600467A/xx unknown
-
1988
- 1988-04-05 SG SG226/88A patent/SG22688G/en unknown
- 1988-04-27 KE KE3813A patent/KE3813A/xx unknown
- 1988-07-28 HK HK568/88A patent/HK56888A/xx unknown
- 1988-09-02 CY CY1431A patent/CY1431A/en unknown
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Legal Events
| Date | Code | Title | Description |
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| MKEC | Expiry (correction) | ||
| MKEX | Expiry |