FI79098C - Foerfarande foer framstaellning av nya, analgetiskt aktiva 3,3-dialkylindolinderivat. - Google Patents
Foerfarande foer framstaellning av nya, analgetiskt aktiva 3,3-dialkylindolinderivat. Download PDFInfo
- Publication number
- FI79098C FI79098C FI830137A FI830137A FI79098C FI 79098 C FI79098 C FI 79098C FI 830137 A FI830137 A FI 830137A FI 830137 A FI830137 A FI 830137A FI 79098 C FI79098 C FI 79098C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- alkoxy
- indoline
- dimethyl
- accordance
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000012458 free base Substances 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 238000005661 deetherification reaction Methods 0.000 claims description 8
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 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 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 52
- 239000007858 starting material Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
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- 150000002476 indolines Chemical class 0.000 description 15
- 238000003756 stirring Methods 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
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- 239000011541 reaction mixture Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 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
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- QWHYSBHTCJIXPO-UHFFFAOYSA-N 5-methoxy-3,3-dimethyl-1h-indol-2-one Chemical compound COC1=CC=C2NC(=O)C(C)(C)C2=C1 QWHYSBHTCJIXPO-UHFFFAOYSA-N 0.000 description 3
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- 229910010082 LiAlH Inorganic materials 0.000 description 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 2
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- 230000000202 analgesic effect Effects 0.000 description 2
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- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000007789 gas Substances 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
- 210000000548 hind-foot Anatomy 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine 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
- 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
- 238000004519 manufacturing process Methods 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
- 239000011707 mineral Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- KXNYJKMZLXNEJD-UHFFFAOYSA-N n-bromo-n-(3-hydroxy-4-methylphenyl)-2-methylpropanamide Chemical compound CC(C)C(=O)N(Br)C1=CC=C(C)C(O)=C1 KXNYJKMZLXNEJD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 239000012730 sustained-release form 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
- 238000005690 transetherification 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 | ||
| CH37382 | 1982-01-21 | ||
| CH374582 | 1982-06-17 | ||
| CH374582 | 1982-06-17 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI830137A0 FI830137A0 (fi) | 1983-01-14 |
| FI830137L FI830137L (fi) | 1983-07-22 |
| FI79098B FI79098B (fi) | 1989-07-31 |
| FI79098C true FI79098C (fi) | 1989-11-10 |
Family
ID=25684383
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI830137A FI79098C (fi) | 1982-01-21 | 1983-01-14 | Foerfarande foer framstaellning av nya, analgetiskt aktiva 3,3-dialkylindolinderivat. |
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 |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: SANDOZ AG |