DE2113343A1 - Indolo- (2,3) - quinolones - prepd by reaction of keto-indoles and anthranilates, followed by dehydration - Google Patents
Indolo- (2,3) - quinolones - prepd by reaction of keto-indoles and anthranilates, followed by dehydrationInfo
- Publication number
- DE2113343A1 DE2113343A1 DE19712113343 DE2113343A DE2113343A1 DE 2113343 A1 DE2113343 A1 DE 2113343A1 DE 19712113343 DE19712113343 DE 19712113343 DE 2113343 A DE2113343 A DE 2113343A DE 2113343 A1 DE2113343 A1 DE 2113343A1
- Authority
- DE
- Germany
- Prior art keywords
- indolo
- alkyl
- quinolones
- mol
- oxindole
- 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.)
- Pending
Links
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 title claims abstract description 6
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical class C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 title 1
- 230000018044 dehydration Effects 0.000 title 1
- 238000006297 dehydration reaction Methods 0.000 title 1
- XXENJDSQBDRHCO-UHFFFAOYSA-N pyrido[3,2-c]carbazol-2-one Chemical class N1=C2C=CC=CC2=C2C1=CC=C1C=CC(=O)N=C12 XXENJDSQBDRHCO-UHFFFAOYSA-N 0.000 title 1
- -1 NaH Chemical class 0.000 claims abstract description 21
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 150000004678 hydrides Chemical class 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 150000004820 halides Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 8
- 150000007660 quinolones Chemical class 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 150000005623 oxindoles Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 230000001085 cytostatic effect Effects 0.000 abstract description 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 229940088710 antibiotic agent Drugs 0.000 abstract 1
- 239000000824 cytostatic agent Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 238000010561 standard procedure Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- 229910052799 carbon Inorganic materials 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- GVOWHGSUZUUUDR-UHFFFAOYSA-N methyl N-methylanthranilate Chemical compound CNC1=CC=CC=C1C(=O)OC GVOWHGSUZUUUDR-UHFFFAOYSA-N 0.000 description 6
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 5
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RSQUAQMIGSMNNE-UHFFFAOYSA-N 1-methyl-3h-indol-2-one Chemical compound C1=CC=C2N(C)C(=O)CC2=C1 RSQUAQMIGSMNNE-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- AQZGPSLYZOOYQP-UHFFFAOYSA-N Diisoamyl ether Chemical compound CC(C)CCOCCC(C)C AQZGPSLYZOOYQP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- MADIORROAVEFIE-UHFFFAOYSA-N indolo[2,3-b]quinolin-1-one Chemical compound N1=C2C=CC=CC2=C2C1=NC1=CC=CC(=O)C1=C2 MADIORROAVEFIE-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- XHTRHEMAXFRQDD-UHFFFAOYSA-N 4-methyl-N-(4-methylbenzoyl)iminobenzamide Chemical compound C1=CC(C)=CC=C1C(=O)N=NC(=O)C1=CC=C(C)C=C1 XHTRHEMAXFRQDD-UHFFFAOYSA-N 0.000 description 1
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 1
- PADRJAARRGWQKM-UHFFFAOYSA-N C1=C2C3=CC=CC=C3N=C2N(C)C2=C1C(=O)CC=C2 Chemical compound C1=C2C3=CC=CC=C3N=C2N(C)C2=C1C(=O)CC=C2 PADRJAARRGWQKM-UHFFFAOYSA-N 0.000 description 1
- 102100031044 Coiled-coil domain-containing protein 13 Human genes 0.000 description 1
- 101000777341 Homo sapiens Coiled-coil domain-containing protein 13 Proteins 0.000 description 1
- RHOWRLMYPPNJBO-UHFFFAOYSA-N O=C1CC=CC2=C1C=C1C3=CC=CC=C3N(C)C1=N2 Chemical compound O=C1CC=CC2=C1C=C1C3=CC=CC=C3N(C)C1=N2 RHOWRLMYPPNJBO-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- MRQIXHXHHPWVIL-UHFFFAOYSA-N chembl1397023 Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC1=CC=CC=C1 MRQIXHXHHPWVIL-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Abstract
Description
Indolo [2.3 - b3 chinolone. und Verfahren zu ihrer Herstellung Gegenstand der Erfindung sind Indolo r2.3 - b3 chinolone und Verfahren zu ihrer Herstellung. Die Verbindungen besitzen eine gewisse Wirksamkeit auf das Zentralnervensystem und können als Antibiotikum und Cystostaticum zur Anwendung gelangen.Indolo [2.3 - b3 quinolones. and process for their manufacture subject of the invention are indolo r2.3 - b3 quinolones and processes for their preparation. The compounds have a certain effectiveness on the central nervous system and can be used as an antibiotic and cystostatic.
Die erfindungsgemässe Verbindung besitzt die folgende Struktur worin R1 ein H-Atom oder eineO-Alkylgruppe, R2-ein H-Atom, ein Alkyl- oder Acyl-Rest und R3 ein H-Atom oder eine Alkvl-Gruppe sein können. Als Alkyl-Rest kommen vor allem solche nlit 1 - 4 C-Atonen und die Benzyl-Gruppe in Frage; als Acyl-Rest dienen die Acetyl-Gruppe sowie vor allem die Benzoyl-Gruppe, gegebenenfalls substituiert mit llalogen und/oder Alkyl oder O-Alkyl-Gruppen, z.B. also die p-Chlorbenzoyl- oder die Methoxybenzoyl-Gruppe.The compound of the present invention has the following structure where R1 can be an H atom or an O-alkyl group, R2 can be an H atom, an alkyl or acyl radical and R3 can be an H atom or an alkyl group. Particularly suitable alkyl radicals are those having 1-4 carbon atoms and the benzyl group; the acetyl group and, above all, the benzoyl group, optionally substituted by halogen and / or alkyl or O-alkyl groups, for example the p-chlorobenzoyl or methoxybenzoyl group, serve as the acyl radical.
Es wurde nun gefunden, dass diese neuen Verbindungen dadurch erhalten werden, dass Oxindole (I)2 der weiter unten aufgeführten STruktur-Formel, worin R² und R² die vorstehend genannte Bedeutung besitzen, mit einem Anthranilsäureester (II), worin R3 die vorstehend angegebene Bedeutung besitzt, und R einen beliebigen Alkyl-Rest darstellt, in Gegenwart von Alkalihydrid in einem Lösungsmittel wie folgt umgesetzt und die gebildeten 3-(2'-Amino-benzoyl)-oxindole (III) mit wasserabspaltenden Mitteln behandelt werden. It has now been found that these new compounds are obtained by treating oxindoles (I) 2 of the structure formula given below, in which R² and R² have the abovementioned meaning, with an anthranilic acid ester (II) in which R3 has the abovementioned meaning and R is any alkyl radical, reacted in the presence of alkali hydride in a solvent as follows and the 3- (2'-amino-benzoyl) -oxindoles (III) formed are treated with dehydrating agents.
Als Lösungsmittel eignen sich z.B. Dioxan, Tetrahydrofuran, Dimethylformamid und höher siedende äther, wie insbesondere der Diisoamyläther. Wasserabspaltende Mittel sind bekanntlich starke Säuren, wie Chlorwasserstoff/Methanol, Schwefelsäure/ Eisessig und Polyphosphorsäure.Suitable solvents are, for example, dioxane, tetrahydrofuran, dimethylformamide and higher-boiling ethers, such as diisoamyl ether in particular. Dehydrating agents Agents are known to be strong acids such as hydrogen chloride / methanol, sulfuric acid / Glacial acetic acid and polyphosphoric acid.
Nach einer Variante des Verfahrens lassen sich die Indolo [2.3 - b3 chinolone mit R2 = Acyl und R3 = Alkyl auch dadurch herstellen, dass erfindungsgemässe Verbindungen (Formel IV) mit R2 = H und R3 = Alkyl mit Säurehalogeniden und Alkalihydrid in Gegenwart eines Lösungsmittels, z.B. Dioxan, Tetrahydrofuran, Dimethylformamid, höher siedende Äther und dergleichen umgesetzt werden.According to a variant of the process, the indolo [2.3 - b3 Quinolones with R2 = acyl and R3 = alkyl also produce that according to the invention Compounds (formula IV) with R2 = H and R3 = alkyl with acid halides and alkali hydride in the presence of a solvent, e.g. dioxane, tetrahydrofuran, dimethylformamide, higher boiling ethers and the like are implemented.
Weiterhin ist es möglich, in die Indolo r2.3 - b3 chinolone mit R2 = H durch Alkylierung, z.B. mittels Alkyl-Halogeniden und Alkali-Alkoholat die Alkylgruppe R² nachträglich einzuführen.It is also possible to convert quinolones into the indolo r2.3 - b3 with R2 = H by alkylation, e.g. by means of alkyl halides and alkali alcoholate the alkyl group R² to be introduced subsequently.
Die Herstellung der einzelnen erfindungsgemässen Verbindungen und der zu diesen Verbindungen führenden Zwischenprodukte sei anhand der Beispiele näher erläutert: Beispiel 1 3-(2dAmino-benzoyl)-oxindol 6,65 g Oxindol (0,05 Mol) werden zu einer Suspension von 4,8 g Natriumhydrid (0,2 Mol) in 70 ml absolutem Dioxan gegeben. Nach Zugabe von 2 Tropfen abs. Methanol wird 7,55 g Anthranilsäuremethylester (0,05 Mol) zugetropft und das Gemisch 8 Stdn.The preparation of the individual compounds according to the invention and the intermediates leading to these compounds are explained in more detail using the examples illustrated: Example 1 3- (2d-amino-benzoyl) -oxindole 6.65 g of oxindole (0.05 mol) become to a suspension of 4.8 g of sodium hydride (0.2 mol) in 70 ml of absolute dioxane given. After adding 2 drops of abs. Methanol becomes 7.55 g of anthranilic acid methyl ester (0.05 mol) was added dropwise and the mixture for 8 hours.
rückfliessend erhitzt. Anschliessend wird zur Trockene eingeengt, der Rückstand in Äther suspendiert und abgesaugt. Das Natriumsalz wird in kalte 5 %ige Schwefelsäure gegeben und das Produkt mit Äther extrahiert. Der Extrakt wird zur Entfernung von Anthranilsäure mit 5tiger NaHCO3-Lösung anschliessend ntit 5 @iger Na2CO3 -Lösung ausgeschüttelt. Nach Ansäuern fällt das 3-(2'-Arnino-benzoyl)-oxindol aus.heated to reflux. It is then concentrated to dryness, the residue suspended in ether and filtered off with suction. The sodium salt is in cold Given 5% sulfuric acid and extracted the product with ether. The extract will to remove anthranilic acid with 5% NaHCO3 solution then ntit 5 @iger Na2CO3 solution shaken out. After acidification, the 3- (2'-amino-benzoyl) -oxindole precipitates the end.
Gel alu Nadeln; Ausbeute 30 %, Schmp. 136-37 (aus Isopropanol und
Ligroin)
C15H12N202 (252,3)
UV (Dioxan): # max = 370 / 314 / 266 / 231 nm (log # = 3,89/3,88/ 4,10/4,37) Beispiel 2 1-Methyl-3-(2-amino-benzoyl)-oxindol Die Darstellung erfolgt analog 3-(2-Amino-benzovl)-oxindol, als Lösungsmittel wird abs. Xylol verwendet.UV (dioxane): # max = 370/314/266/231 nm (log # = 3.89 / 3.88 / 4.10 / 4.37) Example 2 1-Methyl-3- (2-aminobenzoyl) -oxindole The representation takes place analogous to 3- (2-amino-benzovl) oxindole, abs. Xylene used.
Eingesetzte Mengen: 7,35 g N-Methyloxindol (0,05 Mol) 7,55 g Anthranilsäuremethylester (0,05 Mol) 4,8 g NaH (0, 2 Mol) 70 ml abs Xylol Gelbe Nadeln; Ausbeute 40 %; Schmp. : 172-73° (aus Methanol und Ligroin) C16H14N2O2 (266,3) JR (KBr) : 3465/3345 cm-1 (NH), 1640-1610 (C=O), 1595 (C=C).Amounts used: 7.35 g of N-methyloxindole (0.05 mol), 7.55 g of methyl anthranilate (0.05 mol) 4.8 g NaH (0.2 mol) 70 ml abs xylene yellow needles; Yield 40%; M.p. : 172-73 ° (from methanol and ligroin) C16H14N2O2 (266.3) JR (KBr): 3465/3345 cm-1 (NH), 1640-1610 (C = O), 1595 (C = C).
NMR (CDCl3) : 6,7 - 7,6 (m) (arom.H, Nil2, OH) 5,4 (s) (-CO-CH-CO-) 3,38 und 3,26 (s/s) (NCH3) UV (Dioxan) : # max 363 / 313,314 / 267,268 / nm (log # = = 3,92 / 3,95 / 4,18).NMR (CDCl3): 6.7 - 7.6 (m) (arom. H, Nil2, OH) 5.4 (s) (-CO-CH-CO-) 3.38 and 3.26 (s / s) (NCH3) UV (dioxane): # max 363 / 313.314 / 267.268 / nm (log # = = 3.92 / 3.95 / 4.18).
Beispiel 3 3-(2-Methylamino-benzoyl)-oxindol Die Darstellung erfolgt analog (3-(2'-Amino-benzoyl)-oxindol. Example 3 3- (2-Methylamino-benzoyl) -oxindole The representation takes place analogous to (3- (2'-amino-benzoyl) -oxindole.
Eingesetzte Mengen: 6,65 g Oxindol (0,05 Mol) 8,25 g N-Methylanthranilsäuremethylester (0,05 Mol) 4,8 g NaH (0,2 Mol) 70 ml Tetrahydrofuran Gelbe Nadeln; Ausbeute 75 t Schmp. 160-61° (aus Methanol) C16H14N202 (266,3) JR (KBr) : 3425 cm-¹ (RN-CH3), 3195 (NH), 1650 - 1600 (C=O u. C-C), NMR (CDCl3) ; 9,13 ppm (s) (NH) ; 6,6 - 7,7 (m) (arom.H, H3C - NH-, OH) ; 5,45 (s) (-CO - CH - CO) ; 2,88 (s) (NCH3) 1 : > 9 : < 1 : 3 DV (Dioxan) : # max = 380 / 311 / 233 nm (log # = 3,88 / 3,89 / 4,39).Amounts used: 6.65 g of oxindole (0.05 mol), 8.25 g of N-methylanthranilic acid methyl ester (0.05 mol) 4.8 g NaH (0.2 mol) 70 ml tetrahydrofuran Yellow needles; Yield 75 t M.p. 160-61 ° (from methanol) C16H14N202 (266.3) JR (KBr): 3425 cm-1 (RN-CH3), 3195 (NH), 1650-1600 (C = O & C-C), NMR (CDCl3); 9.13 ppm (s) (NH); 6.6 - 7.7 (m) (arom.H, H3C - NH-, OH); 5.45 (s) (-CO-CH-CO); 2.88 (s) (NCH3) 1:> 9: <1: 3 DV (dioxane): # max = 380/311/233 nm (log # = 3.88 / 3.89 / 4.39).
Beispiel 4 l-Methyl-3- (2-methylamino-benzoyl) -oxindol Die Darstellung erfolgt analog 3-(2-Amino-benzoyl)-oxindol. Example 4 1-Methyl-3- (2-methylamino-benzoyl) -oxindole The illustration takes place analogously to 3- (2-amino-benzoyl) -oxindole.
Eingesetzte Mengen: 2,94 g N-Methyloxindol (0,02 Mol) 3,3 g N-Methylanthranilsäuremethylester (0,02 Mol) 1,44 g KH (0,06 Mol) 30 ml Dimethylformamid Gelbe Nadeln; Ausbeute 41 % Schmp. 157-58° (aus Methanol) C17H16N2O2 (280,3) IR (KBr): 3380 cm-1 (NH), 1630 - 1610 (C = O), 1590 (C = C) NMR (CDCl3) : 6,7 - 8,0 (m) (arom.H, -NH-, OH), 5,4 (s) (-CO-CH-CO-); 3,37 und 3,25 (s/s) (NCH3); 2,85 (s) (-HN-CH3) > 9 : <1 : 3 : 3 UV (Dioxan):# max = 380 / 312 / 269 / 232 nm (log # = 3,85 / 3,93 / 4,19 / 4,39) Beispiel 5 3-(2-Methylamino-benzoyl]-5-methoxy-oxindol Die Darstellung erfolgt analog den in 5-Stellung unsubstituierten Oxindolderivaten.Amounts used: 2.94 g of N-methyloxindole (0.02 mol), 3.3 g of N-methylanthranilic acid methyl ester (0.02 mol) 1.44 g KH (0.06 mol) 30 ml dimethylformamide yellow needles; Yield 41 % M.p. 157-58 ° (from methanol) C17H16N2O2 (280.3) IR (KBr): 3380 cm-1 (NH), 1630 - 1610 (C = O), 1590 (C = C) NMR (CDCl3): 6.7-8.0 (m) (arom.H, -NH-, OH), 5.4 (s) (-CO-CH-CO-); 3.37 and 3.25 (s / s) (NCH3); 2.85 (s) (-HN-CH3)> 9: <1 : 3: 3 UV (dioxane): # max = 380/312/269/232 nm (log # = 3.85 / 3.93 / 4.19 / 4.39) Example 5 3- (2-Methylamino-benzoyl) -5-methoxy-oxindole Die Representation is analogous to the oxindole derivatives unsubstituted in the 5-position.
Eingesetzte Mengen: 4,9 g 5-Methoxyindol (0,03 Mol) 4,95 g N-Methylanthranilsäuremethylester (0,03 Mol) 2,88 g NaH (0,12 Mol) 100 ml Diisoamyläther Gelbe Nadeln; Ausbeute: 62 % Schmp. 138-39° (aus Methanol) C17Hl6N203 (296,3) JR (KBr) : 3440 cm-¹ (-NH-CH3), 3170 - 3150 (NH), 1650 - 1610 (C = 0).Amounts used: 4.9 g of 5-methoxyindole (0.03 mol) 4.95 g of N-methylanthranilic acid methyl ester (0.03 mol) 2.88 g NaH (0.12 mol) 100 ml diisoamyl ether yellow needles; Yield: 62 % M.p. 138-39 ° (from methanol) C17Hl6N203 (296.3) JR (KBr): 3440 cm-1 (-NH-CH3), 3170-3150 (NH), 1650-1610 (C = 0).
NMR (CDCl3): 9,25 ppm (s) (NH) ; 7,6 - 6,5 ppm (m) (arom.H,-NH-OH) ; 5,4 (s) (-CO-CH-CO-) ; 3,69 u. 3,60 (s/s) $OCH3); 2,85 (s) (NCH3); 1 : 8 : < 1 : 3 : 3.NMR (CDCl3): 9.25 ppm (s) (NH); 7.6 - 6.5 ppm (m) (arom. H, -NH-OH) ; 5.4 (s) (-CO-CH-CO-); 3.69 & 3.60 (s / s) $ OCH3); 2.85 (s) (NCH3); 1: 8: < 1: 3: 3.
UV (Dioxan) : 2 max = 388 / 315 / 276 nm (log # = 3,95 / 3,94 / 4,27) Beispiel 6 Indolo [2,3 - b] chinolon Eine Lösung von 2,52 g 3-(2'-Amino-benzoyl)-oxindol (0,01) in 80 ml Chlorwasserstoff gesättigtem Methanol wird 15 Stdn. rückfliessend erhitzt. Die Lösung wird anschliessend auf ca. 50 ml eingeengt. Beim Erkalten fiel die gewünschte Verbindung auso Farblose Kristalle: Ausbeute 86 % Schmp. >360° (aus Isopropanol) C15H10N2O (234,3 Ber.: 76,91 % C 4,30 % H 11,96 % N Gef. : 76,90 % C 4,12 % H 11,87 % N JR (KBr) : 3200 cm-1 (NH), 1630 - 1600 (C = O), UV (Dioxan): max = 345 / 329 / 298 / 247 / 228 (log # = 4,43 / 4,31 / 4,09 / 4,74 / 4,70).UV (dioxane): 2 max = 388/315/276 nm (log # = 3.95 / 3.94 / 4.27) example 6 Indolo [2,3 - b] quinolone A solution of 2.52 g of 3- (2'-amino-benzoyl) -oxindole (0.01) in 80 ml of saturated hydrogen chloride is refluxed for 15 hours heated. The solution is then concentrated to approx. 50 ml. When it cooled down, it fell the desired compound from Colorless crystals: yield 86% mp> 360 ° (from isopropanol) C15H10N2O (234.3 calc .: 76.91% C 4.30% H 11.96% N found: 76.90 % C 4.12% H 11.87% N JR (KBr): 3200 cm-1 (NH), 1630 - 1600 (C = O), UV (dioxane): max = 345/329/298/247/228 (log # = 4.43 / 4.31 / 4.09 / 4.74 / 4.70).
Beispiel 7 6-Methyl-indolo [2,3 - b] chinolon Die Darstellung erfolgt analog Indolo C2,3 - b3 chinolon. Example 7 6-methyl-indolo [2,3 - b] quinolone The representation takes place analogous to indolo C2,3 - b3 quinolone.
Eingesetzte Mengen: 2,66 g 1-Methyl-3-(2-amino-benzoyl)-oxindol (0,01 Mol) 80 ml HCl-gesättigtes Methanol 15 Stdn. Erhitzen unter Rückfluss.Amounts used: 2.66 g of 1-methyl-3- (2-aminobenzoyl) oxindole (0.01 Mol) 80 ml of HCl-saturated methanol for 15 hours. Heating under reflux.
Farblose Nadeln; Ausbeute 53 % Schmp. 337-38° (aus Isopropanol C16H12N20 (248,3 Ber.: 77,40 % C 4,87 % H 11,28 % N Gef.: 76,94 % C 5,00 % H 11,32 % N JR (KBr): 3000 - 2810 cm 1 (NH), 1650-1630 (C=O), 1605 (C=C).Colorless needles; Yield 53%, melting point 337-38 ° (from isopropanol C16H12N20 (248.3 calc .: 77.40% C 4.87% H 11.28% N found: 76.94% C 5.00% H 11.32% N JR (KBr): 3000-2810 cm -1 (NH), 1650-1630 (C = O), 1605 (C = C).
NMR (CF3COOH): 8,56 - 8,23 / 8,06 - 7,12 ppm (m/m) (arom.H); 4,1 (s) (NCH3).NMR (CF3COOH): 8.56-8.23 / 8.06-7.12 ppm (m / m) (arom.H); 4.1 (s) (NCH3).
UV (Dioxan) : max = 347 / 331 / 298 / 251 / 231 nm (log # = 4,41 / 4,32 / 4,07 / 4,75 / 4,62 Beispiel 8 5-Methyl-indolo [2,3 - b] chinolon Die Darstellung erfolgt analog Indolo [2,3 - b] chinolon.UV (dioxane): max = 347/331/298/251/231 nm (log # = 4.41 / 4.32 / 4.07 / 4.75 / 4.62 Example 8 5-methyl-indolo [2,3 - b] quinolone The representation is analogous to indolo [2,3 - b] quinolone.
Eingesetzte Mengen: 2,66 g 3-(2-Methylamino-benzoyl)-oxindol (0,01 Mol) 80 ml Tripolyphosphorsäure 15 Stdn. Erhitzen unter Rückfluss, Umkristallisation aus Isopropanol.Amounts used: 2.66 g of 3- (2-methylaminobenzoyl) oxindole (0.01 Mol) 80 ml of tripolyphosphoric acid for 15 hours. Heating under reflux, recrystallization from isopropanol.
Farblose Kristalle; Ausbeute: 79 % ab 320° Zersetzung C16H12N2O (248,3) Ber.: 77, 40 % C 4,87 % H 11,28 % N Gef.: 77,36 % C 4,87 % H 11,46 % N JR (KBr): 3230 - 3180 (NH), 1625 - 1595 (C = 0), NMR (CF3COOH): : 8,23 - 7,16 ppm (m) (arom.H); 4,08 (s) (NCH3).Colorless crystals; Yield: 79% from 320 ° decomposition C16H12N2O (248.3) Calc .: 77, 40% C 4.87% H 11.28% N Found: 77.36% C 4.87% H 11.46% N JR (KBr): 3230-3 180 (NH), 1625-1595 (C = 0), NMR (CF3COOH):: 8.23-7.16 ppm (m) (arom.H); 4.08 (s) (NCH3).
UV (Dioxan):#max = 348 / 331 / 299 / 251 / 228 nm (log # = 4,37 / 4,26 / 4,05 / 4,73 / 4,65).UV (dioxane): # max = 348/331/299/251/228 nm (log # = 4.37 / 4.26 / 4.05 / 4.73 / 4.65).
Beispiel 9 5,6-Dimethyl-indolo g2,3 - b] chinolon 2,8 g 1-Methyl-3-(2-methylamino-benzoyl)-oxindol (0,01 Mol) werden 15 Stdn. in 80 ml chlorwasserstoffgesättigtem Methanol rtckfliessend erhitzt. Die Lösung wurde nach Erkalten in Eiswasser gegossen, der Niederschlag abgesaugt, getrocknet und aus Tetrachlorkohlenstoff und anschliessend aus Äthanol umkristallisiert. Example 9 5,6-Dimethyl-indolo g2,3 - b] quinolone 2.8 g of 1-methyl-3- (2-methylamino-benzoyl) -oxindole (0.01 mol) are refluxed for 15 hours in 80 ml of methanol saturated with hydrogen chloride heated. After cooling, the solution was poured into ice water, the precipitate sucked off, dried and made from carbon tetrachloride and then from ethanol recrystallized.
Farblose Blättchen; Ausbeute 83,5 % Schmp. 2350 (aus Tetrachlorkohlenstoff
und Äthanol C17H14N2O (262,3) Ber.: 77,84 % C 5,38 % H 10,68 % N Gef.: 78,20 % C
5,64 % H 11,09 % N
NMR (CF3COOD): 8,57 - 8,3 / 8,11 - 7,1 ppm (m/m) (arom.H), 4,0 / 3,93 (s/s) (NCH3 / NCH3).NMR (CF3COOD): 8.57-8.3 / 8.11-7.1 ppm (m / m) (arom.H), 4.0 / 3.93 (s / s) (NCH3 / NCH3).
UV (Dioxan): #max = 349 / 333 / 300 / 253 / 232 nm (log # = 4,38 / 4,29 / 4,04 / 4,76 / 4,61) Beispiel 10 5-Methyl-9-methoxy-indolo [2,3 -b] chinolon Die Darstellung erfolgt analog Indolo 52,3 - b3 chinolon.UV (dioxane): #max = 349/333/300/253/232 nm (log # = 4.38 / 4.29 / 4.04 / 4.76 / 4.61) Example 10 5-methyl-9-methoxy-indolo [2,3 -b] quinolone The representation is analogous to indolo 52,3 - b3 quinolone.
Eingesetzte Mengen: 2,96 g 3-(2-Methylamino-benzoyl)-5-methoxy-oxindol (0,01 Mol) 80 ml HCl-gesätigtes Äethanol Schwach gelbe Nadeln; Ausbeute: 75% Schmp. 274° C17H14N2O2 (278,3) Ber.: 73,37 % C 5,07 % H 10,06 % N Gef.: 72,46 % C .5,13 % H 9,36 % N JR(KBr): 3225 - 3180 cm 1 (NH), 1620 - 1600 (C = O).Amounts used: 2.96 g of 3- (2-methylamino-benzoyl) -5-methoxy-oxindole (0.01 mol) 80 ml of HCl-saturated ethanol. Pale yellow needles; Yield: 75% m.p. 274 ° C17H14N2O2 (278.3) calc .: 73.37% C 5.07% H 10.06% N found: 72.46% C. 5.13 % H 9.36% N JR (KBr): 3225-3 180 cm -1 (NH), 1620-1600 (C = O).
NMR (CF3COOH): 8,33 - 7,03 ppm (m) (arom.H); 4,2 (s) (OCH3); 4,06 (s) (NCH3).NMR (CF3COOH): 8.33-7.03 ppm (m) (arom.H); 4.2 (s) (OCH3); 4.06 (s) (NCH3).
UV (Dioxan):# = 355 / 339 / 308 / 254 / 230 nm (log # = 4,42 / 4,32 / 4,08 / 4,61 / 4,67).UV (dioxane): # = 355/339/308/254/230 nm (log # = 4.42 / 4.32 / 4.08 / 4.61 / 4.67).
Beispiel 11 5,6-Dimethyl-9-methoxy-indolo [2,3 - b] chinolon 5-Methyl-9-methoxy-indolo C2,3 - b] chinolon (0,01 Mol) wird mit Methyljodid (0,03 Mol) und Natriumäthanolat (0,01 Mol) 4 Stdn. rückfliessend erhitzt. Das beim Erkalten ausfallende Produkt wird abgesaugt und aus Äthanol umkristallisiert: Schwach gelbe Nadeln; Ausbeute: 81 % Schmp. 225 - 260 C18H16N2O2 (292,3) Bex.: 73,95 % C 5,52 % H 9,58 % N Gef.: 74,09 % C 5-,78 % H 9,38 % N JR(KBr): 1625 cm (C = 0) NMR (CCDC13): 8,17 - 7,84 / 7,5 - 6,92 (m/m) (arom.H); 3,92 (s) (NCH3 u. OCH3); 3,65 (s) (NCH3). Example 11 5,6-Dimethyl-9-methoxy-indolo [2,3-b] quinolone 5-methyl-9-methoxy-indolo C2,3-b] quinolone (0.01 mol) is treated with methyl iodide (0.03 mol) and sodium ethanolate (0.01 mol) heated to reflux for 4 hours. The product that precipitates when it cools is suctioned off and recrystallized from ethanol: pale yellow needles; Yield: 81% m.p. 225 - 260 C18H16N2O2 (292.3) Ex .: 73.95% C 5.52% H 9.58% N Gef .: 74.09% C 5, 78% H 9.38% N JR (KBr): 1625 cm (C = 0) NMR (CCDC13): 8.17-7.84 / 7.5 - 6.92 (m / m) (arom.H); 3.92 (s) (NCH3 &OCH3); 3.65 (s) (NCH3).
UV (Dioxan): #max = 358 / 341 / 309 / 257 / 232 nm (log # = 4,38 / 4,31 / 4,06 / 4,62 / 4,61).UV (dioxane): #max = 358/341/309/257/232 nm (log # = 4.38 / 4.31 / 4.06 / 4.62 / 4.61).
Beispiel 12 5-Methyl-6-(p-Chlorbenzoyl)-9-methoxy-indolo [2,3 - b] chinolon 1,39 g 5-Methyl-9-methoxnr-indolo [2,3 - b] chinolon (0,005 Mol) werden zu einer Suspension von 120 mg NaH (0,005 Mol) in 50 ml abs. Dioxan gegeben. Es wird einige Zeit bei Zimmertemperatur gerührt, dann zum Sieden erhitzt. Die Suspension wird 30 Min. Example 12 5-Methyl-6- (p-Chlorobenzoyl) -9-methoxy-indolo [2,3 - b] quinolone 1.39 g of 5-methyl-9-methoxnr-indolo [2,3 - b] quinolone (0.005 moles) to a suspension of 120 mg of NaH (0.005 mol) in 50 ml of abs. Given dioxane. It is stirred for some time at room temperature, then heated to the boil. The suspension will be 30 min.
im Sieden gehalten. Nach Erkalten werden 0,88 g p-Chlorbenzoylchlorid (0,005 Mol) in 3 ml Dioxan zugetropft und das Gemisch 2 Stdn. rückfliessend erhitzt. Es wird heiss filtriert, das Filtrat zur Trockene eingeengt und aus Isopropanol umkristallisiert: Gelbe Blättchen; Ausbeute 60 z Schmp. 236 - 370 C24H17CIN2O3 (416,9 Ber.: 69,15 % C 4,11 % H 8,50 % Cl 6,72 % N Gef.: 69,31 % C 4,25 z H 8,19 % Cl 6,67 % N JR(KBr) : 1690 und 1635 cm-¹ (C = O).kept simmering. After cooling, 0.88 g of p-chlorobenzoyl chloride are obtained (0.005 mol) in 3 ml of dioxane are added dropwise and the mixture is heated under reflux for 2 hours. It is filtered hot, the filtrate is concentrated to dryness and extracted from isopropanol recrystallized: yellow leaflets; Yield 60 z m.p. 236-370 C24H17CIN2O3 (416.9 Calc .: 69.15% C 4.11% H 8.50% Cl 6.72% N Found: 69.31% C 4.25 z H 8.19% Cl 6.67 % N JR (KBr): 1690 and 1635 cm -1 (C = O).
NMR (CDCl3) : 8,14 - 6-,84 (m) (arom.H) 3,93 (s) (OCH3) ; 3,88 (s) (NCH3).NMR (CDCl3): 8.14-6.84 (m) (arom.H) 3.93 (s) (OCH3); 3.88 (s) (NCH3).
UV (Dioxan) : # max = 340 / 309 / 249 / 223 nm (log # = 4,18 / 4,14 / 4,73 / 4,67).UV (dioxane): # max = 340/309/249/223 nm (log # = 4.18 / 4.14 / 4.73 / 4.67).
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712113343 DE2113343A1 (en) | 1971-03-19 | 1971-03-19 | Indolo- (2,3) - quinolones - prepd by reaction of keto-indoles and anthranilates, followed by dehydration |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19712113343 DE2113343A1 (en) | 1971-03-19 | 1971-03-19 | Indolo- (2,3) - quinolones - prepd by reaction of keto-indoles and anthranilates, followed by dehydration |
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|---|---|
| DE2113343A1 true DE2113343A1 (en) | 1972-09-21 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712113343 Pending DE2113343A1 (en) | 1971-03-19 | 1971-03-19 | Indolo- (2,3) - quinolones - prepd by reaction of keto-indoles and anthranilates, followed by dehydration |
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| DE (1) | DE2113343A1 (en) |
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- 1971-03-19 DE DE19712113343 patent/DE2113343A1/en active Pending
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