DE3246980A1 - Process for the preparation of sulphoximines - Google Patents
Process for the preparation of sulphoximinesInfo
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- DE3246980A1 DE3246980A1 DE19823246980 DE3246980A DE3246980A1 DE 3246980 A1 DE3246980 A1 DE 3246980A1 DE 19823246980 DE19823246980 DE 19823246980 DE 3246980 A DE3246980 A DE 3246980A DE 3246980 A1 DE3246980 A1 DE 3246980A1
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- 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
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- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
Description
Verfahren zur Herstellung von Sulfoximinen Process for the preparation of sulfoximines
[Zusatz zum DBP (Aktenzeichen: P 31 29 444.8)1 Gegenstand der vorliegenden Erfindung ist ein neues Verfahren zur Herstellung von Sulfoximinen der allgemeinen Formel welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere antithrombotische und antimetastatische Wirkungen.[Addition to DBP (file number: P 31 29 444.8) 1 The present invention relates to a new process for the preparation of sulfoximines of the general formula which have valuable pharmacological properties, in particular antithrombotic and antimetastatic effects.
In der obigen allgemeinen Formel I bedeutet A eine gegebenenfalls durch eine oder zwei Alkylgruppen mit jeweils 1 bis 3 Kohlenstoffatomen substituierte Methylen-, Vinylen- oder Äthylengruppe, B eine geradkettige oder verzweigte Alkylengruppe mit 2 bis 6 Kohlenstoffatomen und R1 eine gegebenenfalls durch eine Phenylgruppe substituierte Alkylgruppe mit 1 bis 3 Kohlenstoffatomen oder eine Phenylgruppe, wobei der Phenylkern jeweils durch eine Alkylgruppe mit 1 bis 4 Kohlenstoffatomen, ein Halogenatom, eine Alkoxygruppe mit 1 bis 3 Kohlenstoffatomen, eine Cyclohexyl-, Phenyl- oder Halogenphenylgruppe substituiert sein kann, eine Alkylgruppe mit 4 bis 7 Kohlenstoffatomen, eine Cycloalkylgruppe mit 3 bis 7 Kohlenstoffatomen, eine durch Alkylgruppen mit 1 bis 4- Kohlenstoffatomen, Alkoxygruppen mit 1 bis 3 Kohlenstoffatomen und/oder Halogenatome di- oder trisubstituierte Phenyl- oder disubstituierte Hydroxyphenyl- oder Aminophenylgruppe, wobei die Substituenten des Phenylkerns gleich oder verschieden sein können, eine gegebenenfalls durch eine Alkoxygruppe mit 1 bis 3 Kohlenstoffatomen substituierte Naphthylgruppe oder eine Pyridylgruppe.In the above general formula I, A denotes an optional substituted by one or two alkyl groups each having 1 to 3 carbon atoms Methylene, vinylene or ethylene group, B a straight-chain or branched alkylene group with 2 to 6 carbon atoms and R1 optionally with a phenyl group substituted alkyl group with 1 to 3 carbon atoms or a phenyl group, the phenyl nucleus in each case by an alkyl group having 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 3 carbon atoms, a cyclohexyl, Phenyl or halophenyl group can be substituted, an alkyl group with 4 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, one by alkyl groups with 1 to 4 carbon atoms, alkoxy groups with 1 to 3 carbon atoms and / or halogen atoms di- or trisubstituted phenyl or disubstituted hydroxyphenyl or aminophenyl group, where the substituents of the phenyl nucleus are identical or different may be, one optionally through an alkoxy group having 1 to 3 carbon atoms substituted naphthyl group or a pyridyl group.
Unter den bei der Definition des Restes R1 erwähnten Halogenatomen ist insbesondere ein Fluor-, Chlor- oder Bromatom zu verstehen.Among the halogen atoms mentioned in the definition of the radical R1 is to be understood in particular as a fluorine, chlorine or bromine atom.
FUr die bei der Definition der Reste A, B und R1 eingangs erwähnten Bedeutungen kommt beispielsweise für A die Bedeutung der Methylen-, Methylmethylen-, Dimethylmethylen-, Diäthylmethylen-, Dipropylmethylen-, Vinylen-, Methyl-vinylen- oder Äthylengruppe, für B die der Äthylen-, n-Propylen-, n-Butylen-, n-Pentylen-, n-Hexylen-, l-Methyl-äthylen-, 2-Methyl-äthylen-, l-Methyl-n-propylen-, 2-Methyl-n-propylen-, 3-Methyl-n-propylen-, l-Methyl-n-butylen-, 2-Methyl-n-butylen-, 3-Methyl-n-butylen-, 4-Methyl-nbutylen-, l-Methyl-n-pentylen-, 2-Methyl-n-pentylen-, 3-Methyl-n-pentylen-, 4-Methyl-n-pentylen-, 5-Methyl-n-pentylen-, l,l-Dimethyl-äthylen-, 1,2-Dimethyl-äthylen-, 2,2-Dimethyl-äthylen-, l,1-Dimethyl-n-propylen-, 2,2-Dimethyl-n-propylen-, 3,3-Dimethyl-n-propylen-, 1,2-Dimethyl-n-propylen-, 1,2-Dimethyl-n-propylen-, l,l-Dimethyl-n-butylen-, 2,2-Dimethyl-n-butylen-, 3,3-Dimethyl-n-butylen-, 4 ,4-Dimethyl-n-butylen-, 1 ,2-Dimethyl-n-butylen-, 1,3-Dimethyl-n-butylen-, 1,4-Dimethyl-n-butylen-, 2,3-Dimethyl-n-butylen-, l-Äthyl-äthylen-, 2-Äthyl-äthlen-, l-Äthyl-n-propylen-, 2-Athyl-n-propylen-, 3-Äthyl-n-propylen-, l-Äthyl-n-butylen-, 2-Äthyl-n-butylen-, 3-Äthyl-n-butylen-, 4-Äthyl-nbutylen-, 1-Methyl-2-äthyl-äthylen-, 1-Methyl-2-äthyl-n-propylen-, l-Methyl-3-äthyl-n-propylen-, l-Methyl-2-propyl-äthylen-, l-Propyl-äthylen-, 1-Butyl-äthylen- oder l-Propyl-n-propylengruppe und für R1 die der Methyl-, Äthyl-, Propyl-, Isopropyl-, Butyl-, Isobutyl-, tert.Butyl-, Pentyl-, Neopentyl-, tert.Pentyl-, Hexyl-, Heptyl-, Benzyl-, l-Phenyläthyl-, 2-Phenyläthyl-, l-Phenylpropyl-, 3-Phenylpropyl-, Fluorbenzyl-, Chlorbenzyl-, Brombenzyl-, Methylbenzyl-, Isopropylbenzyl-, Methoxybenzyl-, Äthoxybenzyl-, Cyclopropyl-, Cyclobutyl-, Cyclopentyl-, Cyclohexyl-, Cycloheptyl-, Phenyl-, Fluorphenyl-, Chlorphenyl-, Bromphenyl-, Methylphenyl-, Dimethylphenyl-, Isopropylphenyl-, tert.Butylphenyl-, Methoxyphenyl-, Äthoxyphenyl-, Propoxyphenyl-, Cyclohexylphenyl-, Biphenylyl-, Fluorphenyl-phenyl-, Chlorphenyl-phenyl-, Difluorphenyl-, Dichlorphenyl -, Dibromphenyl-, Dimethoxyphenyl-, Methoxychlorphenyl-, Methoxy-bromphenyl-, Methyl-tert.butyl-phenyl-, Methyl-chlorphenyl-, Methyl-bromphenyl-, ter t. Butyl-bromphenyl-, Dichlor -aminophenyl-, Dibrom-aminophenyl-, Dimethyl-aminophenyl-, Dichlor-hydroxyphenyl-, Dibrom-hydroxyphenyl-, Dimethyl-hydroxyphenyl-, Di-tert.butyl-hydroxyphnyl-, Trimethoxy-phenyl-, Naphthyl-, Methoxynaphthyl-oder Pyridylgruppe in Betracht.For those mentioned at the beginning in the definition of the radicals A, B and R1 Meanings come, for example, for A the meaning of methylene, methylmethylene, Dimethylmethylene, diethylmethylene, dipropylmethylene, vinylene, methyl vinylene or ethylene group, for B the ethylene, n-propylene, n-butylene, n-pentylene, n-hexylene, l-methyl-ethylene, 2-methyl-ethylene, l-methyl-n-propylene, 2-methyl-n-propylene, 3-methyl-n-propylene, l-methyl-n-butylene, 2-methyl-n-butylene, 3-methyl-n-butylene, 4-methyl-n-butylene, l-methyl-n-pentylene, 2-methyl-n-pentylene, 3-methyl-n-pentylene, 4-methyl-n-pentylene, 5-methyl-n-pentylene, l, l-dimethyl-ethylene, 1,2-dimethyl-ethylene, 2,2-dimethyl-ethylene, l, 1-dimethyl-n-propylene, 2,2-dimethyl-n-propylene, 3,3-dimethyl-n-propylene, 1,2-dimethyl-n-propylene, 1,2-dimethyl-n-propylene, l, l-dimethyl-n-butylene, 2,2-dimethyl-n-butylene-, 3,3-dimethyl-n-butylene-, 4,4-dimethyl-n-butylene-, 1,2-dimethyl-n-butylene-, 1,3-dimethyl-n-butylene, 1,4-dimethyl-n-butylene, 2,3-dimethyl-n-butylene, l-ethyl-ethylene, 2-ethyl-ethylene-, l-ethyl-n-propylene-, 2-ethyl-n-propylene-, 3-ethyl-n-propylene-, l-ethyl-n-butylene, 2-ethyl-n-butylene, 3-ethyl-n-butylene, 4-ethyl-n-butylene, 1-methyl-2-ethyl-ethylene, 1-methyl-2-ethyl-n-propylene, l-methyl-3-ethyl-n-propylene, l-methyl-2-propyl-ethylene, l-propyl-ethylene, 1-butyl-ethylene or l-propyl-n-propylene group and for R1 the the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, Neopentyl, tert-pentyl, hexyl, heptyl, benzyl, l-phenylethyl, 2-phenylethyl, l-phenylpropyl, 3-phenylpropyl, fluorobenzyl, chlorobenzyl, bromobenzyl, methylbenzyl, Isopropylbenzyl, methoxybenzyl, ethoxybenzyl, cyclopropyl, cyclobutyl, cyclopentyl, Cyclohexyl, cycloheptyl, phenyl, fluorophenyl, chlorophenyl, bromophenyl, methylphenyl, Dimethylphenyl, isopropylphenyl, tert-butylphenyl, methoxyphenyl, ethoxyphenyl, Propoxyphenyl-, cyclohexylphenyl-, biphenylyl-, fluorophenyl-phenyl-, chlorophenyl-phenyl-, Difluorophenyl, dichlorophenyl -, dibromophenyl, dimethoxyphenyl, Methoxychlorophenyl-, methoxy-bromophenyl-, methyl-tert-butyl-phenyl-, methyl-chlorophenyl-, Methyl-bromophenyl-, ter t. Butyl-bromophenyl-, dichloro-aminophenyl-, dibromo-aminophenyl-, Dimethyl-aminophenyl-, dichloro-hydroxyphenyl-, dibromo-hydroxyphenyl-, dimethyl-hydroxyphenyl-, Di-tert-butyl-hydroxyphnyl, trimethoxyphenyl, naphthyl, methoxynaphthyl or Pyridyl group into consideration.
Bevorzugte Verbindungen der obigen allgemeinen Formel I sind diejenigen, in denen A eine Dimethylmethylen-, Vinylen- oder Äthylengruppe, B eine geradkettige Alkylengruppe mit 3 bis 5 Kohlenstoffatomen und R1 eine Alkylgruppe mit 1 bis 6 Kohlenstoffatomen, eine Benzyl-, Phenyläthyl-, Cyclohexyl-, Naphthyl-, Methoxy-naphthyl- oder Pyridylgruppe, eine gegebenenfalls durch eine Alkylgruppe mit 1 bis 4 Kohlenstoffatomen, eine Methoxy-, Cyclohexyl-, Phenyl-oder Fluorphenylgruppe, ein Fluor-, Chlor- oder Bromatom substituierte Phenylgruppe, eine durch Alkylgruppen mit 1 bis 4 Kohlenstoffatomen, Methoxygruppen, Chlor- und/oder Bromatome disubstituierte Phenylgruppen, wobei die Substituenten des.Preferred compounds of the above general formula I are those in which A is a dimethylmethylene, vinylene or ethylene group, B a straight-chain Alkylene group having 3 to 5 carbon atoms and R1 is an alkyl group having 1 to 6 Carbon atoms, a benzyl, phenylethyl, cyclohexyl, naphthyl, methoxy-naphthyl- or pyridyl group, optionally substituted by an alkyl group with 1 to 4 carbon atoms, a methoxy, cyclohexyl, phenyl or fluorophenyl group, a fluorine, chlorine or A phenyl group substituted by a bromine atom, an alkyl group with 1 to 4 carbon atoms, Methoxy groups, chlorine and / or bromine atoms, disubstituted phenyl groups, the Substituents of the.
Phenylkerns gleich oder verschieden sein können, oder eine durch zwei Chlor- oder Bromatome, zwei Methoxygruppen oder zwei Alkylgruppen mit jeweils 1 bis 4 Kohlenstoffatomen substituierte Aminophenyl-, Hydroxyphenyl- oder Methoxyphenylgruppe bedeuten. Phenyl nucleus can be the same or different, or one by two chlorine or bromine atoms, two methoxy groups or two alkyl groups each having 1 to 4 carbon atoms substituted aminophenyl, hydroxyphenyl or methoxyphenyl group mean.
Besonders bevorzugte Verbindungen der obigen allgemeinen Formel 1 sind jedoch diejenigen, in denen A eine Dimethylmethylen-, Vinylen- oder Äthylengruppe, B eine n-Butylengruppe und R1 eine Methyl- oder Methoxynaphthylgruppe, eine gegebenenfalls durch eine Methoxygruppe, ein Fluor-oder Chloratom substituierte Phenylgruppe, eine durch zwei Chlor- oder Bromatome substituierte Phenylgruppe, eine Methyl-bromphenyl-, 4-Amino-3,5-dibrom-phenyl- oder Di-tert.butyl-hydroxy-phenylgruppe pe bedeuten.Particularly preferred compounds of the above general formula 1 are however those in which A is a dimethylmethylene, vinylene or ethylene group, B. an n-butylene group and R1 a methyl or methoxynaphthyl group, one optionally by a methoxy group, a fluorine or chlorine atom substituted phenyl group, a phenyl group substituted by two chlorine or bromine atoms, a methyl bromophenyl, 4-Amino-3,5-dibromophenyl or di-tert-butyl-hydroxyphenyl group are pe.
Erfindungsgemäß erhält man die Verbindungen der allgemeinen Formel I durch Hydrolyse einer Verbindung der allgemeinen Formel in der A, B und R1 wie eingangs definiert sind und R einen hydrolytisch abspaltbaren Acylrest darstellt.According to the invention, the compounds of the general formula I are obtained by hydrolysis of a compound of the general formula in which A, B and R1 are as defined at the outset and R represents an acyl radical which can be hydrolytically split off.
Als Acylrest kommt beispielsweise der einer Carbonsäure oder eines Kohlensäurederivates wie die Acetyl-, Propionyl-, Butanoyl-, Benzoyl-, Pinanoyl-, Nicotinoyl-, Äthoxycarbonyl-, Aminocarbonyl- oder Dimethylaminocarbonylgruppe in Betracht.An example of an acyl radical is that of a carboxylic acid or one Carbonic acid derivatives such as acetyl, propionyl, butanoyl, benzoyl, pinanoyl, Nicotinoyl, ethoxycarbonyl, aminocarbonyl or dimethylaminocarbonyl group in Consideration.
Die Hydrolyse wird in Gegenwart einer Säure oder Base, z.B.The hydrolysis is carried out in the presence of an acid or base, e.g.
in Gegenwart von Salzsäure, Schwefelsäure, Natronlauge, Kalilauge oder Kaliumcarbonat, in einem Lösungsmittel oder Lösungsmittelgemisch wie Wasser, Methanol, Wasser/Methanol, Wasser/Äthanol oder Wasser/Tetrahydrofuran bei Temperaturen bis zur Siedetemperatur des verwendeten Lösungsmittels, z.B.in the presence of hydrochloric acid, sulfuric acid, sodium hydroxide solution, potassium hydroxide solution or potassium carbonate, in a solvent or solvent mixture such as water, Methanol, water / methanol, water / ethanol or water / tetrahydrofuran at temperatures up to the boiling point of the solvent used, e.g.
bei Temperaturen zwischen 50 und 900C, durchgeführt.at temperatures between 50 and 900C carried out.
Die als Ausgangsstoffe verwendeten Verbindungen der allgemeinen Formel II erhält man nach literaturbekannten Verfahren, beispielsweise durch Umsetzung einer entsprechenden Hydroxyverbindungen mit einem entsprechenden Halogenid vorzugsweise in Gegenwart eines aprotischen Lösungsmittels und einer Alkalibase. Das hierfür erforderliche Halogenid erhält man durch Oxidation eines entsprechenden Thioäthers, anschließende Umsetzung mit einem entsprechenden O-Mesitylensulfonylhydroxylamin und anschließende Acylierung.The compounds of the general formula used as starting materials II is obtained by processes known from the literature, for example by reaction a corresponding hydroxy compound with a corresponding halide is preferred in the presence of an aprotic solvent and an alkali base. That for this required halide is obtained by oxidation of a corresponding thioether, subsequent reaction with a corresponding O-mesitylenesulfonylhydroxylamine and subsequent acylation.
Wie bereits eingangs erwähnt, weisen die Verbindungen der allgemeinen Formel I wertvolle pharmakologische Eigenschaften auf, insbesondere antithrombotische Wirkungen. Diese steigern die Synthese des aggregationshemmenden Prostaglandins I2, außerdem weisen sie eine Hemmwirkung auf die Tumormetastasierung auf.As already mentioned at the beginning, the compounds have the general Formula I has valuable pharmacological properties, especially antithrombotic Effects. These increase the synthesis of the aggregation-inhibiting prostaglandin I2, they also have an inhibitory effect on tumor metastasis.
Die nachfolgenden Beispiele sollen die Erfindung näher erläutern: Beispiel A 6-[4-(N-Acetyl-3,4-dichlorphenylsulfoximino)-butoxyl-3,4-dihydro-carbostyril 3,4-Dichlorphenylsulfinyl-4-brombutan wird mit O-Mesitylensulfonylhydroxylamin zu 3 ,4-Dichlor-phenylsulfoximino-4-brombutan umgesetzt und anschließend mit Acetanhydrid in 3,4-Dichlorphenyl- (N-acetyl-sulfoximino)-4-brombutan überführt.The following examples are intended to explain the invention in more detail: Example A 6- [4- (N-acetyl-3,4-dichlorophenylsulfoximino) -butoxyl-3,4-dihydro-carbostyril 3,4-dichlorophenylsulfinyl-4-bromobutane is added with O-mesitylenesulfonylhydroxylamine 3, 4-dichloro-phenylsulfoximino-4-bromobutane reacted and then with acetic anhydride converted into 3,4-dichlorophenyl- (N-acetyl-sulfoximino) -4-bromobutane.
Schmelzpunkt: 170-l730C, Ausbeute: 98 % der Theorie.Melting point: 170-173 ° C., yield: 98% of theory.
163,2 mg (0,001 Mol) 6-Hydroxycarbostyril, gelöst in 2 ml Dimethylsulfoxid, werden mit 448 mg (0,0013 Mol) 3,4-Dichlorphenyl-(N-acetyl-sulfoximino)-4-brombutan und 276,3 mg (0,002 Mol) wasserfreiem Kaliumcarbonat versetzt und 17 Stunden lang bei Zimmertemperatur gerührt. Danach wird portionsweise in kleinen Anteilen mit Wasser versetzt, worauf das Reaktionsprodukt in weißen Nadeln auskristallisiert.163.2 mg (0.001 mol) 6-hydroxycarbostyril, dissolved in 2 ml dimethyl sulfoxide, are with 448 mg (0.0013 mol) of 3,4-dichlorophenyl- (N-acetyl-sulfoximino) -4-bromobutane and 276.3 mg (0.002 mol) of anhydrous potassium carbonate are added and Stirred for 17 hours at room temperature. Then it is made in small portions Fractions mixed with water, whereupon the reaction product crystallizes out in white needles.
Schmelzpunkt: 149-1510C, Ausbeute: 267,1 mg (62,5 % der Theorie).Melting point: 149-1510C, yield: 267.1 mg (62.5% of theory).
Analog lassen sich folgende Verbindungen herstellen: 6-[4-(N-Carbamoyl-3,4-dichlorphenylsulfoximino)-butoxyl-3,4-dihydroxycarbostyril Schmelzpunkt: 148-1500C 6-[4-(N-Butyryl-3,4-dichlorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 133-1350C 6-t4-lN-Pivaloyl-3,4-dichlorphenylsulfoximino)-butoxy1-3,4-dihydrocarbostyril Schmelzpunkt: 158-160°C 6-[4-(N-(2-Methoxyacetyl)-3,4-dichlorphenylsulfoximino)-butoxy] -3 ,4-dihydrocarbostyril Schmelzpunkt: 103-1050C 6-[4-(N-Benzoyl-3,4-dichlorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: llO-111°C 6-[4-(N-(4-Methoxybenzoy 3,4-dichlorphenylsulfoximino)-butoxyl-3,4-dihydroycarbostyril Schmelzpunkt: 101-1030C 6-[4-(N-Nicotinoyl-3,4-dichlorphenylsulfoximino)-butoxyl-3, 4-dihydrocarbostyr il Schmelzpunkt: 101-1030C 6-[4-(N-(2-Acetoxy-phenylacetyl)-3,4-dichlorphenylsulfoximino)-butoxyl -3,4-dihydrocarbostyril Rf-Wert: 0,2 (Kieselgelplatte, Äthylenchlorid) 5-[4-(N-Acetyl-3,4-dimethoxyphenylsulfoximìno)-butoxyl-3,3-dimethyl-indolin-2-on Rf-Wert: 0,3 (Kieselgelplatte, Äthylenchlorid/Äthanol = 9:1) 5-C4-(N-Butyryl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethyl-indolin-2-on RfWert: 0,35 (Kieselgelplatte, Essigester/Methylenchlorid = 1:1) 5-f4-(N-Pivaloyl-3,4-dimethoxyphenylsulfoximino)-butoxy/-3,3-dimethyl-indolin-2-on Rf-wert: 0,45 (Kieselgelplatte, Essigester/Methylenchlorid =1:1) 5-[4-(N-Carbamoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethyl-indolin-2-on Rf-Wert: 0,25 (Kieselgelplatte, Athylenchlorid/Äthanol = 9:1) 5-[4-(N-Dimethylaminocarbonyl-3,4-dimethoxyphenylSulfoximino)-butoxyl-3,3-dimethyl-indolin-2-on Rf-Wert: 0,3 (Kieselgelplatte, Äthylenchlorid/thanol = 9:1) 5-[4-(N-(4-Chlorbenzoyl)-3,4-dìmethoxyphenylsulfoximino)-butoxyl-3,3-dimethyl-indolin-2-on Schmelzpunkt: 174-1770C 5-[4-(N-Nicotinoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethyl-indolin-2-on Rf-Wert: 0,25 (Kieselgelplatte, Äthylenchlorid/Äthanol = 9:1) 6-[4-(N-Benzoyl-4-fluorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 64-680C 6-[4-(N-(4-Chlorbenzoyl)-4-fluorphenylsulfoximino)-butoxy]-3, 4-dihydrocarbostyr il Schmelzpunt: 134-1380C 6-f4-(N-2-Thenoyl-3,4-dichlorphenlsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 100-1020C 6-[4-(N-(+)-Pinanoyl-3,4-dichlorphenylsulfoximino)-butoxy]-i 3,4-dihydrocarbostyril Schmelzpunkt: 69-740C 6-[4-(N-(-)-Pinanoyl-3,4-dichlorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 69-740C 6-[4-(N-Acetyl-4-fluorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Rf-Wert: 0,65 (Kieselgel, Laufmittel: Äthylenchlorid/ Äthanol = 85:15) 6-[4-(N-Butyroyl-4-fluorphenylsulfoximino)-butoxy] -3,4-dihydrocarbostyril Rf -Wert: 0,70 (Kieselgel, Laufmittel: Äthylenchlorid/ Äthanol = 85:15) 6-[4-(N-(+)-Pinanoyl-4-fluorphenylsulfoximino)-butoxyl-3,4-dihydrocarbostyril Schmelzpunkt: 116-1200C 6-[4-(N-(-)-Pinanoyl-4-fluorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 122-1230C Beispiel 1 6-[4-(4-Fluorphenylsulfoximino)-butoxyi-3'4-dihydrocarbostyril 108 mg (0,0002 Mol) 6-[4-(N-(+)-Pinanoyl-4-fluorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril werden mit 2 ml 2n wässrig/äthanolischer Kalilauge (84,5 b Äthanol enthaltend) 2 Stunden lang im Ölbad auf 80°C erhitzt. Man neutralisiert mit 5n Salzsäure, engt im Vakuum bis zur Trockne ein und extrahiert den erhaltenen Salzkuchen mit Methylenchlorid.The following compounds can be prepared analogously: 6- [4- (N-Carbamoyl-3,4-dichlorophenylsulfoximino) -butoxyl-3,4-dihydroxycarbostyril Melting point: 148-1500C 6- [4- (N-Butyryl-3,4-dichlorophenylsulfoximino) -butoxy] -3,4-dihydrocarbostyril Melting point: 133-1350C 6-t4-IN-pivaloyl-3,4-dichlorophenylsulfoximino) -butoxy1-3,4-dihydrocarbostyril Melting point: 158-160 ° C 6- [4- (N- (2-methoxyacetyl) -3,4-dichlorophenylsulfoximino) butoxy] -3, 4-dihydrocarbostyril Melting point: 103-1050C 6- [4- (N-Benzoyl-3,4-dichlorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 110-111 ° C 6- [4- (N- (4-Methoxybenzoy 3,4-dichlorophenylsulfoximino) -butoxyl-3,4-dihydroycarbostyril Melting point: 101-1030C 6- [4- (N-nicotinoyl-3,4-dichlorophenylsulfoximino) -butoxyl-3, 4-dihydrocarbostyrene melting point: 101-1030C 6- [4- (N- (2-acetoxyphenylacetyl) -3,4-dichlorophenylsulfoximino) butoxyl -3,4-dihydrocarbostyril Rf value: 0.2 (silica gel plate, ethylene chloride) 5- [4- (N-acetyl-3,4-dimethoxyphenylsulfoximino) -butoxyl-3,3-dimethyl-indolin-2-one Rf value: 0.3 (silica gel plate, ethylene chloride / ethanol = 9: 1) 5-C4- (N-butyryl-3,4-dimethoxyphenylsulfoximino) butoxy] -3,3-dimethyl-indolin-2-one Rf value: 0.35 (silica gel plate, ethyl acetate / methylene chloride = 1: 1) 5-f4- (N-pivaloyl-3,4-dimethoxyphenylsulfoximino) -butoxy / -3,3-dimethyl-indolin-2-one Rf value: 0.45 (silica gel plate, ethyl acetate / methylene chloride = 1: 1) 5- [4- (N-carbamoyl-3,4-dimethoxyphenylsulfoximino) butoxy] -3,3-dimethyl-indolin-2-one Rf value: 0.25 (silica gel plate, ethylene chloride / ethanol = 9: 1) 5- [4- (N-dimethylaminocarbonyl-3,4-dimethoxyphenylsulfoximino) -butoxyl-3,3-dimethyl-indolin-2-one Rf value: 0.3 (silica gel plate, ethylene chloride / ethanol = 9: 1) 5- [4- (N- (4-chlorobenzoyl) -3,4-di-methoxyphenylsulfoximino) -butoxyl-3,3-dimethyl-indoline-2 -on Melting point: 174-1770C 5- [4- (N-nicotinoyl-3,4-dimethoxyphenylsulfoximino) butoxy] -3,3-dimethyl-indolin-2-one Rf value: 0.25 (silica gel plate, ethylene chloride / ethanol = 9: 1) 6- [4- (N-Benzoyl-4-fluorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 64-680C 6- [4- (N- (4-chlorobenzoyl) -4-fluorophenylsulfoximino) -butoxy] -3, 4-dihydrocarbostyril melting point: 134-1380C 6-f4- (N-2-thenoyl-3,4-dichlorophenlsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 100-1020C 6- [4- (N - (+) - Pinanoyl-3,4-dichlorophenylsulfoximino) -butoxy] -i 3,4-dihydrocarbostyril Melting point: 69-740C 6- [4- (N - (-) - Pinanoyl-3,4-dichlorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 69-740C 6- [4- (N-acetyl-4-fluorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Rf value: 0.65 (silica gel, mobile phase: ethylene chloride / ethanol = 85:15) 6- [4- (N-butyroyl-4-fluorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Rf value: 0.70 (silica gel, mobile phase: ethylene chloride / ethanol = 85:15) 6- [4- (N - (+) - Pinanoyl-4-fluorophenylsulfoximino) -butoxyl-3,4-dihydrocarbostyril Melting point: 116-1200C 6- [4- (N - (-) - Pinanoyl-4-fluorophenylsulfoximino) -butoxy] -3,4-dihydrocarbostyril Melting point: 122-1230C Example 1 6- [4- (4-Fluorophenylsulfoximino) -butoxyi-3'4-dihydrocarbostyril 108 mg (0.0002 moles) 6- [4- (N - (+) - pinanoyl-4-fluorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril with 2 ml of 2N aqueous / ethanolic potassium hydroxide solution (containing 84.5 b of ethanol) 2 Heated in an oil bath at 80 ° C for hours. It is neutralized with 5N hydrochloric acid and concentrated in vacuo to dryness and extracted the salt cake obtained with methylene chloride.
Nach Trocknen der organischen Phase über Natriumsulfat wird das Lösungsmittel im Vakuum entfernt und der erhaltene Rückstand aus Äthanol umkristallisiert.After drying the organic phase over sodium sulfate, the solvent becomes removed in vacuo and the residue obtained recrystallized from ethanol.
Schmelzpunkt: 170-1730C Ausbeute: 64,5 mg (86 % der Theorie).Melting point: 170-1730C Yield: 64.5 mg (86% of theory).
Die Hydrolyse kann auch mit 2,5 n Salzsäure durchgeführt werden.The hydrolysis can also be carried out with 2.5N hydrochloric acid.
Beispiel 2 6-[4-(3,4-Dichlorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Hergestellt analog Beispiel 1 durch Hydrolyse von 6-[4-(N-Acetyl-3,4-dichlorphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril mit methanolischer Kalilauge.Example 2 6- [4- (3,4-dichlorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Prepared analogously to Example 1 by hydrolysis of 6- [4- (N-acetyl-3,4-dichlorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril with methanolic potassium hydroxide solution.
Schmelzpunkt: 163-1650C Ausbeute: 89 % der Theorie.Melting point: 163-1650C Yield: 89% of theory.
Beispiel 3 6- F4- (4-Fluorphenylsulfoximino) -butoxyi -3 ,4-dihydrocarbostyril Hergestellt analog Beispiel 1 durch Hydrolyse von 6-[4-(N-Benzoyl-4-fluorphenylsulfoxirnino)-butoxyi -3'4-dihydrocarbostyril mit äthanolischer Kalilauge.Example 3 6- F4- (4-fluorophenylsulfoximino) -butoxyi -3, 4-dihydrocarbostyril Prepared analogously to Example 1 by hydrolysis of 6- [4- (N-benzoyl-4-fluorophenylsulfoxirnino) -butoxyi -3'4-dihydrocarbostyril with ethanolic potassium hydroxide solution.
Schmelzpunkt: 170-1730C Ausbeute: 88 % der Theorie.Melting point: 170-1730C Yield: 88% of theory.
Beispiel 4 6- [4- (4-Fluorphenylsulfoximino) -butöxy] -carbostyril Hergestellt analog Beispiel 1 durch Hydrolyse von 6-[4-(N-Benzoyl-4-fluorphenylsulfoximino)-butoxyj -carbostyril mit äthanolischer Kalilauge.Example 4 6- [4- (4-Fluorophenylsulfoximino) -butoxy] -carbostyril Prepared analogously to Example 1 by hydrolysis of 6- [4- (N-benzoyl-4-fluorophenylsulfoximino) -butoxyj -carbostyril with ethanolic potassium hydroxide solution.
Schmelzpunkt: 176-1780C Ausbeute: 67 % der Theorie.Melting point: 176-1780C Yield: 67% of theory.
Beispiel 5 5-r4-(3,4-Dimethoxyphenylsulfoximino)-butoxyl-3,3-dimethYlindolin-2-on Hergestellt analog Beispiel 1 durch Hydrolyse von 5-[4-(N-Nicotinoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethyl -indolin-2-on mit äthanolischer Kalilauge.Example 5 5-r4- (3,4-Dimethoxyphenylsulfoximino) -butoxyl-3,3-dimethYlindolin-2-one Prepared analogously to Example 1 by hydrolysis of 5- [4- (N-nicotinoyl-3,4-dimethoxyphenylsulfoximino) butoxy] -3,3-dimethyl -indolin-2-one with ethanolic potassium hydroxide solution.
Schmelzpunkt: 107-1090C Ausbeute: 58 % der Theorie.Melting point: 107-1090C Yield: 58% of theory.
IR-Spektrum: -CO-NH 3430 cm =N-H 3330 cm Beispiel 6 5-[4-(3,4-Dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethylindolin-2-on Hergestellt analog Beispiel 1 durch Hydrolyse von 5-[4-(N-Acetyl-3,4-dimethoxyphenylsulfoximino)-butoxyi -3,3-dimethylindolin-2-on mit wässrig-äthanolischer Salzsäure.IR spectrum: -CO-NH 3430 cm = N-H 3330 cm Example 6 5- [4- (3,4-Dimethoxyphenylsulfoximino) butoxy] -3,3-dimethylindolin-2-one Prepared analogously to Example 1 by hydrolysis of 5- [4- (N-acetyl-3,4-dimethoxyphenylsulfoximino) butoxyi -3,3-dimethylindolin-2-one with aqueous-ethanolic hydrochloric acid.
Schmelzpunkt: 108-1090C Ausbeute: 83 % der Theorie.Melting point: 108-1090C Yield: 83% of theory.
Beispiel 7 5-f4-(3,4-Dimethoxyphenylsulfoximino)-butoxyl-3,3-dimethylindolin-2-on Hergestellt analog Beispiel 1 durch Hydrolyse von 5-[4-(N-Carbamoyl-3,4-dimethoxyphenylsulfoximino)-butoxy]-3,3-dimethyl-indolin-2-on und äthanolischer Kalilauge.Example 7 5-f4- (3,4-Dimethoxyphenylsulfoximino) -butoxyl-3,3-dimethylindolin-2-one Prepared analogously to Example 1 by hydrolysis of 5- [4- (N-carbamoyl-3,4-dimethoxyphenylsulfoximino) butoxy] -3,3-dimethyl-indolin-2-one and ethanolic potassium hydroxide.
Schmelzpunkt: 107-1080C Die Hydrolyse kann auch mit wässrig-äthanolischer Salzsäure durchgeführt werden.Melting point: 107-1080C The hydrolysis can also be done with aqueous-ethanolic Hydrochloric acid can be carried out.
Analog den vorstehenden Beispielen lassen sich folgende Verbindungen herstellen: 6-(4-Phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril Schmelzpunkt: 127-1290C 6-[4-(4-tert.Butylphenylsulfoximino)-butoxy]-3,4-dihydrocarbosytyr il Schmelzpunkt: 201-2030C 6-[4-(3,5-Di-tert.butyl-4-hydroxyphenylsulfoximino)-butoxy] -3,4-dihydrocarbostyril Schmelzpunkt: 110-1120C 4-(4-Cyclohexylphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 174-1760C 6-t4-(4-Biphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 184-1860C 6-[4-(Naphthyl-(2)-sulfoximino)-butoxy]-3,4-dihydrocarbostril Schmelzpunkt: 151-1520C 6-[4-(4-Chlorphenylsulfoximino)-butoxy] -3,4-dihydrocarbostyril Schmelzpunkt: 150-1510C 6-[4-(3-Methyl-4-bromphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 150-1520C 6-[4-(3,5-Dibrom-4-aminophenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 110-1130C 6-(4-Phenylsulfoximino-butoxy)-carbostyril Schmelzpunkt: 161-1620C 6-[4-(4-tert.Butylphenylsulfoximino)-butoxy]-carbostyril Schmelzpunkt: 208-2100C 6-[4-(3,5-Di-tert.butyl-4-hydroxyphenylsulfoximino)-butoxy]-carbostyril Schmelzpunkt: 205-2070C 6-f4-(4-Cyclohexylphenylsulfoximino)-butoxyl-carbostyril Schmelzpunkt.: 195-1970C 6-[4-(4-Biphenylylsulfoximino)-butoxy] carbostyril Schmelzpunkt: 236-2380C 6-(4-Cyclohexylsulfoximino-butoxy)-carbostyril Schmelzpunkt: 145-1470C 6-[4-(4-Chlorphenylsulfoximino)-butoxyl-carbostyril Schmelzpunkt: 20l-2030C 6-[4-(4-Bromphenylsulfoximino)-butoxyl-carbostyril Schmelzpunkt: 211-2130C 6-r4-(3,4-Dichlorphenylsulfoximino)-butoxyl-carbostyril Schmelzpunkt: 214-2160C 6-[4-(3-Methyl-4-bromphenylsulfoximino)-butoxyl-carbostyril Schmelzpunkt: 193-1940C 6-[4-(2'-Fluor-4-biphenylylsulfoximino)-butoxy]-carbostyril Schmelzpunkt: l9l-l930C 6-[4-(3r5-Dibrom-4-aminophenylsulfoximino)-butoxy]-carbostyril Schmelzpunkt: 130-1350C 3,3-Dimethyl-5-[4-(4-methylphenylsulfoximino)-butoxy]-indolin--2-on Schmelzpunkt: l46-1470C 3,3-Dimethyl-5-[4-(4-tert.butylphenylsulfoximino)-butoxyl-indolin-2-on Schmelzpunkt: 195-1970C 3,3-Dimethyl-5-[4-(2-methyl-4-tert.butylphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 149-1500C 3,3-Dimethyl-5-[4-(3,5-di-tert.butyl-4-hydroxyphenylsulfoximino)-butoxy]-indolin-2-on Rf-Wert: 0,25 (Kieselgelplatte, Laufmittel: Essigester/ Methylenchlorid = 1:1) 3,3-Dimethyl-5-(4-cyclohexylphenylsulfoximino-butoxy)-indoli-2-on Schmelzpunkt: 162-1630C 3,3-Dimethyl-5-[4-(2-naphthylsulfoximino)-butoxyl-indolin-2-on Schmelzpunkt: 120-1210C 3,3-Dimethyl-5-(4-cyclohexylsulfoximino-butoxy)-indolin-2-on Schmelzpunkt: 108-1090C 3,3-Dimethyl-5-(4-benzylsulfoximino-butoxy)-indolin-2-on Schmelzpunkt: 98-990C 3,3-Dimethyl-5-[4-(4-fluorphenylsulfoximino)-butoxy]-indolin--2-on Schmelzpunkt: 101-1020C 3,3-Dimethyl-5-[4-(4-chlorphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 136-1370C 3,3-Dimethyl-5-[4-(4-bromphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 160-1610C 3,3-Dimethyl-5-[4-(3,4-dichlorphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 147-1480C 3,3-Dimethyl-5-[4-(2,5-dichlorphenylsulfoximino)-butoxy]-indolin-2-on Rf-Wert: 0,3 (Kieselgelplatte, Laufmittel: Essigester/ Methylenchlorid = 1:1) 3,3-Dimethyl-5-[4-(3-methyl-4-brom-phenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 131-1320C 3,3-Dimethyl-5-[4-(2'-fluor-4-biphenylylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 177-178°C 3,3-Dimethyl-5-[4-(3,5-dibrom-4-aminophenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 202-2040C 3,3-Dimethyl-5-[4-(4-methoxyphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 140-1410C 3,3-Dimethyl-5-14-(2-methoxyphenylsulfoximino)-butoxyl-indolin-2-on RfNert: 0,35 (Kieselgel, Laufmittel: Äthylenchlorid/ Äthanol = 9:1) 3,3-Dimethyl-5-[4-(6-methoxy-naphth-2-yl-sulfoximino)-butoxyl-indolin-2-on Schmelzpunkt: 174-175°C 3,3-Dimethyl-5-(4-phenylsulfoximino-butoxy)-indolin-2-on Schmelzpunkt: lll-1120C 6-[4-(3,4-Dimethoxyphenylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 154-1560C 6-[3-(3,4-Dichlorphenylsulfoximino)-propoxy} -3,4-dihydrocarbostyril Schmelzpunkt: 144-146°C 6-[5-(3,4-Dichlorphenylsulfoximino)-pentoxyl-3,4-dihydrocarbostyril Schmelzpunkt: 154-1550C 6-(3-Rthylsulfoximino-propoxy)-3,4-dihydrocarbostyril Schmelzpunkt: 107-1090C 6-(3-Äthylsulfoximino-propoxy)-carbostyril Schmelzpunkt: 166-1670C 3,3-Dimethyl-5-[4-(3,4-dimethylphenylsulfoximino)-butoxy]-indolin-2-on Schmelzpunkt: 153-1540C 3,3-Dimethyl-5-(4-methylsulfoximino-butoxy)-indolin-2-on Schmelzpunkt: 123-1230C 6-(4-n-Hexylsulfoximino-butoxy)-3,4-dihydrocarbostyril Schmelzpunkt: 111-113°C 6-[4-(2-Phenyläthylsulfoximino)-butoxy]-3,4-dihydrocarbostyril Schmelzpunkt: 158-1590C 5-(4-Phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril Schmelzpunkt: l59-l600C 7-(4-Phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril Schmelzpunkt: 137-1390C 8-(4-Phenylsulfoximino-butoxy)-3,4-dihydrocarbostyril Schmelzpunkt: 78-80°CThe following compounds can be prepared analogously to the above examples prepare: 6- (4-phenylsulfoximino-butoxy) -3,4-dihydrocarbostyril melting point: 127-1290C 6- [4- (4-tert-butylphenylsulfoximino) butoxy] -3,4-dihydrocarbosytyr il Melting point: 201-2030C 6- [4- (3,5-Di-tert.butyl-4-hydroxyphenylsulfoximino) -butoxy] -3,4-dihydrocarbostyril melting point: 110-1120C 4- (4-cyclohexylphenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 174-1760C 6-t4- (4-biphenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 184-1860C 6- [4- (Naphthyl- (2) -sulfoximino) -butoxy] -3,4-dihydrocarbostril Melting point: 151-1520C 6- [4- (4-chlorophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 150-1510C 6- [4- (3-methyl-4-bromophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 150-1520C 6- [4- (3,5-Dibromo-4-aminophenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 110-1130C 6- (4-Phenylsulfoximino-butoxy) -carbostyril Melting point: 161-1620C 6- [4- (4-tert-butylphenylsulfoximino) -butoxy] -carbostyril Melting point: 208-2100C 6- [4- (3,5-di-tert-butyl-4-hydroxyphenylsulfoximino) butoxy] carbostyril Melting point: 205-2070C 6-f4- (4-Cyclohexylphenylsulfoximino) -butoxyl-carbostyril Melting point: 195-1970C 6- [4- (4-Biphenylylsulfoximino) -butoxy] carbostyril Melting point: 236-2380C 6- (4-Cyclohexylsulfoximino-butoxy) -carbostyril Melting point: 145-1470C 6- [4- (4-chlorophenylsulfoximino) -butoxyl-carbostyril Melting point: 20l-2030C 6- [4- (4-bromophenylsulfoximino) -butoxyl-carbostyril Melting point: 211-2130C 6-r4- (3,4-dichlorophenylsulfoximino) -butoxyl-carbostyril Melting point: 214-2160C 6- [4- (3-methyl-4-bromophenylsulfoximino) -butoxyl-carbostyril Melting point: 193-1940C 6- [4- (2'-fluoro-4-biphenylylsulfoximino) -butoxy] -carbostyril Melting point: 191-1930C 6- [4- (3r5-dibromo-4-aminophenylsulfoximino) butoxy] carbostyril Melting point: 130-1350C 3,3-dimethyl-5- [4- (4-methylphenylsulfoximino) butoxy] indolin - 2-one Melting point: 146-1470C 3,3-Dimethyl-5- [4- (4-tert-butylphenylsulfoximino) -butoxyl-indolin-2-one Melting point: 195-1970C 3,3-dimethyl-5- [4- (2-methyl-4-tert-butylphenylsulfoximino) butoxy] indolin-2-one Melting point: 149-1500C 3,3-Dimethyl-5- [4- (3,5-di-tert-butyl-4-hydroxyphenylsulfoximino) -butoxy] -indolin-2-one Rf value: 0.25 (silica gel plate, mobile phase: ethyl acetate / methylene chloride = 1: 1) 3,3-dimethyl-5- (4-cyclohexylphenylsulfoximino-butoxy) indoli-2-one Melting point: 162-1630C 3,3-dimethyl-5- [4- (2-naphthylsulfoximino) -butoxyl-indolin-2-one Melting point: 120-1210C 3,3-dimethyl-5- (4-cyclohexylsulfoximino-butoxy) indolin-2-one Melting point: 108-1090C 3,3-dimethyl-5- (4-benzylsulfoximino-butoxy) indolin-2-one Melting point: 98-990C 3,3-dimethyl-5- [4- (4-fluorophenylsulfoximino) butoxy] indolin-2-one Melting point: 101-1020C 3,3-dimethyl-5- [4- (4-chlorophenylsulfoximino) butoxy] indolin-2-one Melting point: 136-1370C 3,3-Dimethyl-5- [4- (4-bromophenylsulfoximino) butoxy] indolin-2-one Melting point: 160-1610C 3,3-dimethyl-5- [4- (3,4-dichlorophenylsulfoximino) butoxy] indolin-2-one Melting point: 147-1480C 3,3-dimethyl-5- [4- (2,5-dichlorophenylsulfoximino) butoxy] indolin-2-one Rf value: 0.3 (silica gel plate, mobile phase: ethyl acetate / methylene chloride = 1: 1) 3,3-dimethyl-5- [4- (3-methyl-4-bromo-phenylsulfoximino) -butoxy] -indoline-2- on Melting point: 131-1320C 3,3-dimethyl-5- [4- (2'-fluoro-4-biphenylylsulfoximino) -butoxy] -indolin-2-one Melting point: 177-178 ° C 3,3-Dimethyl-5- [4- (3,5-dibromo-4-aminophenylsulfoximino) butoxy] indolin-2-one Melting point: 202-2040C 3,3-dimethyl-5- [4- (4-methoxyphenylsulfoximino) butoxy] indolin-2-one Melting point: 140-1410C 3,3-dimethyl-5-14- (2-methoxyphenylsulfoximino) -butoxyl-indolin-2-one RfNert: 0.35 (silica gel, mobile phase: ethylene chloride / ethanol = 9: 1) 3,3-dimethyl-5- [4- (6-methoxy-naphth-2-yl-sulfoximino) -butoxyl-indolin-2-one Melting point: 174-175 ° C 3,3-dimethyl-5- (4-phenylsulfoximino-butoxy) indolin-2-one Melting point: III-1120C 6- [4- (3,4-Dimethoxyphenylsulfoximino) butoxy] -3,4-dihydrocarbostyril Melting point: 154-1560C 6- [3- (3,4-dichlorophenylsulfoximino) propoxy} -3,4-dihydrocarbostyril Melting point: 144-146 ° C 6- [5- (3,4-dichlorophenylsulfoximino) -pentoxyl-3,4-dihydrocarbostyril Melting point: 154-1550C 6- (3-Rthylsulfoximino-propoxy) -3,4-dihydrocarbostyril Melting point: 107-1090C 6- (3-ethylsulfoximino-propoxy) -carbostyril Melting point: 166-1670C 3,3-dimethyl-5- [4- (3,4-dimethylphenylsulfoximino) -butoxy] -indolin-2-one Melting point: 153-1540C 3,3-dimethyl-5- (4-methylsulfoximino-butoxy) indolin-2-one Melting point: 123-1230C 6- (4-n-hexylsulfoximino-butoxy) -3,4-dihydrocarbostyril melting point: 111-113 ° C 6- [4- (2-Phenyläthylsulfoximino) -butoxy] -3,4-dihydrocarbostyril Melting point: 158-1590C 5- (4-phenylsulfoximino-butoxy) -3,4-dihydrocarbostyril Melting point: 159-1600C 7- (4-Phenylsulfoximino-butoxy) -3,4-dihydrocarbostyril Melting point: 137-1390C 8- (4-phenylsulfoximino-butoxy) -3,4-dihydrocarbostyril melting point: 78-80 ° C
Claims (5)
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019830005853A KR840006964A (en) | 1982-12-18 | 1983-12-10 | How to prepare sulfoximine |
| DK570583A DK570583A (en) | 1982-12-18 | 1983-12-12 | PROCEDURE FOR PREPARING SULFOXIMINES |
| GR73248A GR78783B (en) | 1982-12-18 | 1983-12-14 | |
| FI834578A FI834578A (en) | 1982-12-18 | 1983-12-14 | FREQUENCY FRAMING FOR SULFOXIMINERS. |
| DD83258010A DD216925A5 (en) | 1982-12-18 | 1983-12-15 | PROCESS FOR THE PREPARATION OF SULFOXIMINES |
| AT0437183A AT383593B (en) | 1982-12-18 | 1983-12-15 | METHOD FOR PRODUCING SULFOXIMINES |
| HU834202A HU190515B (en) | 1982-12-18 | 1983-12-16 | Process for producing sulfoximines |
| ES528093A ES8502423A1 (en) | 1982-12-18 | 1983-12-16 | Procedure for the preparation of sulfoximines (Machine-translation by Google Translate, not legally binding) |
| NO834648A NO834648L (en) | 1982-12-18 | 1983-12-16 | ANALOGUE PROCEDURE FOR THE PREPARATION OF PHARMACOLOGICAL ACTIVE SULPHOXIMIN DERIVATIVES |
| CA000443542A CA1201123A (en) | 1982-12-18 | 1983-12-16 | Process for the preparation of sulphoximines |
| PT77837A PT77837B (en) | 1982-12-18 | 1983-12-16 | PROCESS FOR THE PREPARATION OF SULFOXIMINES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813129444 DE3129444A1 (en) | 1981-07-25 | 1981-07-25 | Sulphoximides, their preparation, and medicaments containing these compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3246980A1 true DE3246980A1 (en) | 1984-06-20 |
Family
ID=6137766
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19813129444 Withdrawn DE3129444A1 (en) | 1981-07-25 | 1981-07-25 | Sulphoximides, their preparation, and medicaments containing these compounds |
| DE19823246980 Withdrawn DE3246980A1 (en) | 1981-07-25 | 1982-12-18 | Process for the preparation of sulphoximines |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19813129444 Withdrawn DE3129444A1 (en) | 1981-07-25 | 1981-07-25 | Sulphoximides, their preparation, and medicaments containing these compounds |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS5824559A (en) |
| KR (1) | KR840000491A (en) |
| AR (1) | AR230745A1 (en) |
| AU (1) | AU556082B2 (en) |
| CA (1) | CA1175430A (en) |
| CS (1) | CS236488B2 (en) |
| DD (1) | DD202871A5 (en) |
| DE (2) | DE3129444A1 (en) |
| DK (1) | DK329582A (en) |
| ES (4) | ES514275A0 (en) |
| FI (1) | FI822550L (en) |
| GR (1) | GR76181B (en) |
| HU (1) | HU188188B (en) |
| NO (1) | NO822255L (en) |
| PL (1) | PL137725B1 (en) |
| PT (1) | PT75297A (en) |
| SU (1) | SU1158041A3 (en) |
| YU (1) | YU158182A (en) |
| ZA (1) | ZA825273B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2385118T3 (en) * | 2008-01-17 | 2012-07-18 | Bayer Pharma Aktiengesellschaft | Sulfoximin-substituted quinazoline derivatives as immunomodulators, their preparation and use as medicines |
-
1981
- 1981-07-25 DE DE19813129444 patent/DE3129444A1/en not_active Withdrawn
-
1982
- 1982-06-30 NO NO822255A patent/NO822255L/en unknown
- 1982-07-16 SU SU823463928A patent/SU1158041A3/en active
- 1982-07-20 YU YU01581/82A patent/YU158182A/en unknown
- 1982-07-20 FI FI822550A patent/FI822550L/en not_active Application Discontinuation
- 1982-07-21 PL PL1982237600A patent/PL137725B1/en unknown
- 1982-07-21 AR AR290035A patent/AR230745A1/en active
- 1982-07-21 DD DD82241832A patent/DD202871A5/en unknown
- 1982-07-22 CS CS825591A patent/CS236488B2/en unknown
- 1982-07-22 HU HU822373A patent/HU188188B/en unknown
- 1982-07-22 PT PT75297A patent/PT75297A/en unknown
- 1982-07-22 DK DK329582A patent/DK329582A/en not_active Application Discontinuation
- 1982-07-23 JP JP57128814A patent/JPS5824559A/en active Pending
- 1982-07-23 GR GR68840A patent/GR76181B/el unknown
- 1982-07-23 AU AU86378/82A patent/AU556082B2/en not_active Ceased
- 1982-07-23 CA CA000407915A patent/CA1175430A/en not_active Expired
- 1982-07-23 ZA ZA825273A patent/ZA825273B/en unknown
- 1982-07-23 ES ES514275A patent/ES514275A0/en active Granted
- 1982-07-24 KR KR1019820003316A patent/KR840000491A/en unknown
- 1982-12-18 DE DE19823246980 patent/DE3246980A1/en not_active Withdrawn
-
1983
- 1983-01-07 ES ES518826A patent/ES518826A0/en active Granted
- 1983-01-07 ES ES518828A patent/ES8400412A1/en not_active Expired
- 1983-01-07 ES ES518827A patent/ES8400411A1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| YU158182A (en) | 1984-08-31 |
| DE3129444A1 (en) | 1983-02-10 |
| ES518827A0 (en) | 1983-10-16 |
| PL137725B1 (en) | 1986-07-31 |
| PL237600A1 (en) | 1983-03-28 |
| PT75297A (en) | 1982-08-01 |
| GR76181B (en) | 1984-08-03 |
| CS236488B2 (en) | 1985-05-15 |
| ES518828A0 (en) | 1983-10-16 |
| ES8400410A1 (en) | 1983-10-16 |
| FI822550L (en) | 1983-01-26 |
| CA1175430A (en) | 1984-10-02 |
| HU188188B (en) | 1986-03-28 |
| AU8637882A (en) | 1983-04-14 |
| ES518826A0 (en) | 1983-10-16 |
| KR840000491A (en) | 1984-02-22 |
| ES8305333A1 (en) | 1983-04-01 |
| JPS5824559A (en) | 1983-02-14 |
| ES8400411A1 (en) | 1983-10-16 |
| AR230745A1 (en) | 1984-06-29 |
| ES514275A0 (en) | 1983-04-01 |
| SU1158041A3 (en) | 1985-05-23 |
| FI822550A0 (en) | 1982-07-20 |
| AU556082B2 (en) | 1986-10-23 |
| NO822255L (en) | 1983-01-26 |
| ZA825273B (en) | 1984-03-28 |
| ES8400412A1 (en) | 1983-10-16 |
| DK329582A (en) | 1983-01-26 |
| DD202871A5 (en) | 1983-10-05 |
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