EP0557307A1 - Verfahren zur herstellung von 4,5,6,7-tetrahydro-imidazo-(4,5,ljk) (1,4)-benzodiazepin-2-(1h)-thionen sowie zwischenprodukte - Google Patents
Verfahren zur herstellung von 4,5,6,7-tetrahydro-imidazo-(4,5,ljk) (1,4)-benzodiazepin-2-(1h)-thionen sowie zwischenprodukteInfo
- Publication number
- EP0557307A1 EP0557307A1 EP91918424A EP91918424A EP0557307A1 EP 0557307 A1 EP0557307 A1 EP 0557307A1 EP 91918424 A EP91918424 A EP 91918424A EP 91918424 A EP91918424 A EP 91918424A EP 0557307 A1 EP0557307 A1 EP 0557307A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- hydrogen
- compound
- radical
- compounds
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
Definitions
- the invention relates to 2- [(3-nitro-benzyl) amino] alkyl-a ine and a process for the preparation of 4,5,6,7-tetra-hydro-imidazo- [4,5, ljk] [1.4] -benzodiazepin-2 (IH) thiones via the 2- [(3-nitro-benzyl) amino] alkylamines as intermediates.
- the invention relates to an improved process for the preparation of 4,5,6,7-tetrahydro-imidazo- [4,5, ljk] [1.4] - benzodiazepine-2 (IH) thiones of the general formula I
- R1 is a hydrogen atom or a straight-chain or branched alkyl radical having 1-6 carbon atoms
- R2 represents a hydrogen atom, a straight-chain or branched alkyl radical having 1-6 carbon atoms, a straight-chain or branched alkenyl radical having 3-6 carbon atoms, a C 3 -C 6 alkynyl radical, a C 3 -C 5 cycloalkyl radical or a C ⁇ _-Cg- Alkyl radical which can also be substituted by a phenyl radical or a C3-Cg-cycloalkyl radical, 3 and R4 are identical or different and, independently of one another, denote hydrogen, halogen, hydroxyl, Ci-Cg-alkoxy, Cx-Cg-alkyl or amino.
- R * L represents a hydrogen atom or a straight-chain or branched alkyl group with 1-6 carbon atoms.
- the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl and isohexyl groups are preferred
- 2 can represent a hydrogen atom or a straight-chain or branched C 1 -C 6 -alkyl group.
- the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl and isohexyl group are preferred.
- R2 can also be a straight-chain or branched C3-C6-
- Alkylene group mean.
- the allyl, 2-methylallyl, isobutenyl, pentenyl, isopentenyl, hexenyl and isohexenyl group are preferred.
- R2 can also mean a straight-chain or branched C3-C6 alkynyl group. This means in particular a 2-propynyl, 2-butynyl, 3-butynyl, pentynyl or hexynyl radical.
- a C3 ⁇ C5-C cloalkyl radical for R3 means a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl radical.
- R3 and R4 can be the same or different and independently of one another are hydrogen, halogen, such as fluorine, chlorine or bromine, hydroxy, alkyl, such as methyl or ethyl, or alkoxy, such as methoxy or ethoxy,
- the compounds of general formula I can have one or more
- REPLACEMENT LEAF have asymmetric carbon atoms.
- the invention therefore also relates to all optically active and diastereomeric forms and racemic and diastereomeric mixtures.
- R * j_, 2, R 3 and R4 have the meanings given, are prepared by using a compound of the general formula II,
- R ⁇ _, R 2 , R3 and R4 have the meanings given, according to a conventional method with a reagent which transfers the thiocarbonyl group, such as, for example, carbon disulfide, thiocarbonyldiimidazole, thiophosgene or thiourea.
- a reagent which transfers the thiocarbonyl group such as, for example, carbon disulfide, thiocarbonyldiimidazole, thiophosgene or thiourea.
- R 1, R 2, R 3 and R 4 have the meanings indicated and convert the nitro group into an amino group by a conventional method known to the person skilled in the art.
- the compounds of general formula III can be prepared by using a compound of general
- X represents a halogen atom or a sulfonic ester grouping.
- the compounds of general formula IV can be prepared by using a compound of general formula VI,
- REPLACEMENT LEAF in which R_, 3 and 4 have the meanings given and Y represents a halogen atom, is subjected to a cyclization reaction.
- R] _, R3, R4 and Y have the meanings given, is subjected to a reduction using hydrogen boron or diborane.
- the compounds of the general formula VII can be prepared by using a compound of the general formula VII
- R, R 3 , R4 and Y have the meanings given, and R5 is hydrogen or an alkyl radical, is subjected to an amidation reaction by methods known to those skilled in the art.
- the compounds of the general formula VIII can be prepared by using a compound of the general formula VIII
- Ri has the meanings given and R 5 is hydrogen or an alkyl radical, brings about the reaction in the customary manner.
- the compounds of the general formula IX are known from the literature or can be prepared by methods known from the literature.
- REPLACEMENT LEAF are and relate to racemates or optically active compounds.
- the reactions of the compounds of the general formula II with a reagent transferring a thiocarbonyl group to a compound of the general formula I are carried out by, for example, reacting a compound of the general formula II with carbon disulfide in an aqueous-alcoholic solution in the presence of alkali by a method known to those skilled in the art or by reacting a compound of the general formula II with thiocarbonyldiimidazole in an inert solvent, such as, for example, Dimethylformamide brings to reaction.
- the compounds of the general formula II are prepared by converting the nitro group into an amino group in a compound of the general formula by a method known to those skilled in the art.
- the compounds of the general formula IV are reacted with compounds of the general formula V to give compounds of the general formula III by reacting the compounds of the general formula IV with compounds of the general formula V in an inert solvent, such as, for example, dimethylformamide, dimethylacetamide, acetone, methyl ethyl ketone or alcohol at at temperatures between room temperature and reflux temperature of the solvent, tion agent such as sodium carbonate or potassium carbonate to the skilled person by methods known brings preferably between 40 "C and 60 C in the presence of a ⁇ alkaline Kondensa ⁇ to the reaction.
- an inert solvent such as, for example, dimethylformamide, dimethylacetamide, acetone, methyl ethyl ketone or alcohol
- the cyclization of a compound of general formula VI to a compound of general formula IV can be carried out by using a compound of general Formula VI in an inert solvent such as dimethyl formamide, dimethylacetamide, acetone, methyl ethyl ketone or alcohol in the presence of an alkaline condensing agent such as sodium carbonate or potassium carbonate to react at temperatures between room temperature and the reflux temperature of the solvent.
- an inert solvent such as dimethyl formamide, dimethylacetamide, acetone, methyl ethyl ketone or alcohol
- an alkaline condensing agent such as sodium carbonate or potassium carbonate
- the cyclization reaction of a compound of the general formula VI to a compound of the general formula IV can also be carried out by heating a compound of the general formula IV in the presence of an alkaline condensing agent, such as, for example, sodium carbonate or potassium carbonate, without the addition of a solvent to temperatures between 100 "C and 200 ⁇ C, preferably between 130 ⁇ C and 170 ° C.
- an alkaline condensing agent such as, for example, sodium carbonate or potassium carbonate
- the compounds of the general formula VI are shown in that a compound of the general formula VII with hydrogen boron or diborane in an inert solvent, such as e.g. Tetrahydrofuran, dioxane, diethyl ether or methylene chloride at temperatures between room temperature and reflux temperature of the solvent or by reacting a compound of general formula VI in an inert solvent such as e.g. Subjects methylene chloride reduction with a tetraalkylammonium borohydride.
- an inert solvent such as e.g. Tetrahydrofuran, dioxane, diethyl ether or methylene chloride
- B a borane-ammonia complex, borane-tert-butylamine complex, borane-N, N-diethylaniline complex, borane-dimethylamine complex, borane-4-dimethylaminopyridine complex, borane-dimethyl sulfide complex, borane -Dimethyl sulfide complex, borane-N-ethyldiisopropylamine complex, borane-N-ethylmorpholine complex, borane-2,6-lutidine complex, borane-N-methylmorpholine complex, borane-morpholine complex, borane-1,4 -Oxathian complex, borane-N-phenylmorpholine complex, borane-piperazine complex,
- the compounds of the general formula VII are illustrated by subjecting a compound of the general formula VIII to an amide formation reaction according to the person skilled in the art and methods known from the literature.
- the compounds of general formula VIII can be prepared by reacting a compound of general formula IX with a compound of general formula X by methods known to those skilled in the art.
- the invention relates in particular to a new and economical process for the production of
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4036552 | 1990-11-16 | ||
DE4036552A DE4036552C1 (es) | 1990-11-16 | 1990-11-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0557307A1 true EP0557307A1 (de) | 1993-09-01 |
Family
ID=6418388
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP91918424A Withdrawn EP0557307A1 (de) | 1990-11-16 | 1991-10-29 | Verfahren zur herstellung von 4,5,6,7-tetrahydro-imidazo-(4,5,ljk) (1,4)-benzodiazepin-2-(1h)-thionen sowie zwischenprodukte |
Country Status (9)
Country | Link |
---|---|
EP (1) | EP0557307A1 (es) |
JP (1) | JPH06502400A (es) |
AU (1) | AU8855991A (es) |
CA (1) | CA2096238A1 (es) |
DE (1) | DE4036552C1 (es) |
IE (1) | IE913979A1 (es) |
IL (1) | IL100033A0 (es) |
WO (1) | WO1992008706A1 (es) |
ZA (1) | ZA919050B (es) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ238664A (en) * | 1990-07-06 | 1992-12-23 | Janssen Pharmaceutica Nv | Substituted tetrahydroimidazo(1,4)benzodiazepin-2-(thi)ones and pharmaceutical anti-viral compositions |
US5463049A (en) * | 1991-09-24 | 1995-10-31 | Janssen Pharmaceutica N.V. | Process for preparing enantiomerically pure imidazo[4,5,1-JK][1,4]-benzodiazepin-2(1H)-thiones |
UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8806449D0 (en) * | 1988-03-18 | 1988-04-20 | Janssen Pharmaceutica Nv | Antiviral hexahydroimiazo(1 4)benzodiazepin-2-ones |
IL93136A (en) * | 1989-02-23 | 1995-01-24 | Janssen Pharmaceutica Nv | History of tetrahydroimidazo [1,4] benzodiazepine-2-thione, their preparation and pharmaceutical preparations containing them |
-
1990
- 1990-11-16 DE DE4036552A patent/DE4036552C1/de not_active Expired - Lifetime
-
1991
- 1991-10-29 JP JP3517660A patent/JPH06502400A/ja active Pending
- 1991-10-29 CA CA002096238A patent/CA2096238A1/en not_active Abandoned
- 1991-10-29 EP EP91918424A patent/EP0557307A1/de not_active Withdrawn
- 1991-10-29 WO PCT/EP1991/002038 patent/WO1992008706A1/de not_active Application Discontinuation
- 1991-10-29 AU AU88559/91A patent/AU8855991A/en not_active Abandoned
- 1991-11-11 IL IL100033A patent/IL100033A0/xx unknown
- 1991-11-15 ZA ZA919050A patent/ZA919050B/xx unknown
- 1991-11-15 IE IE397991A patent/IE913979A1/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9208706A1 * |
Also Published As
Publication number | Publication date |
---|---|
ZA919050B (en) | 1992-08-26 |
DE4036552C1 (es) | 1992-02-06 |
AU8855991A (en) | 1992-06-11 |
IL100033A0 (en) | 1992-08-18 |
WO1992008706A1 (de) | 1992-05-29 |
CA2096238A1 (en) | 1992-05-17 |
JPH06502400A (ja) | 1994-03-17 |
IE913979A1 (en) | 1992-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69216251T2 (de) | Substituierte aryl- und heteroaryl-phenyloxazolidinone | |
DE69515390T2 (de) | Ureido-derivate von naphtalenphosphonsäure und verfahren zu ihrer herstellung | |
DE2434911C2 (de) | Phenyläthylamin-Derivate und pharmazeutische Zusammensetzungen | |
DD282686A5 (de) | Verfahren zur herstellung eines benzothiazolderivates | |
EP0287907A1 (de) | Pyrazolo[3,4-d]pyrimidine, Verfahren zu ihrer Herstellung und Verwendung als Arzneimittel | |
DE69715097T2 (de) | Benzimidazol-derivate und ihre Verwendung als Corticotropin freisetzenden Faktor Antagonisten | |
DE1670753A1 (de) | Verfahren zur Herstellung von 2-Cycloalkylaminooxazolinen | |
DE2305092A1 (de) | Alpha-aminomethylbenzylalkoholderivate | |
DE2757680A1 (de) | Neue 2-oxo-1-pyrrolidinessigsaeurederivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel | |
DE2006978B2 (de) | N- [H3-Trifluormethyl-phenyl)-propyl-(2)] -glycinderivate, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
CH626352A5 (en) | Process for the preparation of 2,6-disubstituted 2-phenyliminoimidazolidines and their acid addition salts | |
EP0557307A1 (de) | Verfahren zur herstellung von 4,5,6,7-tetrahydro-imidazo-(4,5,ljk) (1,4)-benzodiazepin-2-(1h)-thionen sowie zwischenprodukte | |
DE69103535T2 (de) | 1-Phenylalkyl-3-Phenylharnstoff-Derivate. | |
EP0012822B1 (de) | Neue 3,4-disubstituierte 2-Phenylimino-imidazolidine, deren Säureadditionssalze, diese enthaltende Arzneimittel und Verfahren zu deren Herstellung | |
DE2609574C3 (de) | 1 -^-Fluor-S-trifluormethylthiophenyD-piperazin, dessen Salze, Verfahren zu dessen Herstellung und Arzneimittel | |
EP0491243A1 (de) | Alkylaminoalkylamin- und -äther- Verbindungen sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
DE2918832A1 (de) | 5,6-dihydro-11-alkylen-morphantridin- 6-one | |
DE2230003A1 (de) | Neue nitrosoharnstoffderivate | |
DE2811131A1 (de) | Imino-benzoxazin- und imino-benzothiazin-derivate sowie verfahren zu deren herstellung | |
DE2601703C2 (de) | 2-(Indenyloxymethyl)morpholin-Derivate | |
DE1046063B (de) | Verfahren zur Herstellung neuer, amoebicid wirkender Acetanilide | |
DE956306C (de) | Verfahren zur Herstellung von neuen Derivaten des Pyrimidins | |
DE2038922A1 (de) | Organische Thiazolopyrimidine | |
DE2742158A1 (de) | Herstellung substituierter harnstoffe | |
DE3710254A1 (de) | Antiulcusmittel |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19930424 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19950503 |