DD235642A1 - PROCESS FOR THE PREPARATION OF 4- (OMEGA-AMINOALKYL) THIAZOLENE - Google Patents
PROCESS FOR THE PREPARATION OF 4- (OMEGA-AMINOALKYL) THIAZOLENE Download PDFInfo
- Publication number
- DD235642A1 DD235642A1 DD27434485A DD27434485A DD235642A1 DD 235642 A1 DD235642 A1 DD 235642A1 DD 27434485 A DD27434485 A DD 27434485A DD 27434485 A DD27434485 A DD 27434485A DD 235642 A1 DD235642 A1 DD 235642A1
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- thiazoles
- aminoalkyl
- general formula
- radical
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract 5
- 150000003557 thiazoles Chemical class 0.000 claims abstract description 15
- -1 methyl halides Chemical class 0.000 claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- 239000007858 starting material Substances 0.000 claims abstract 4
- 239000003814 drug Substances 0.000 claims abstract 2
- 210000004051 gastric juice Anatomy 0.000 claims abstract 2
- 230000002401 inhibitory effect Effects 0.000 claims abstract 2
- 230000028327 secretion Effects 0.000 claims abstract 2
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 2
- 241000251730 Chondrichthyes Species 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- BLNWTAHYTCHDJH-UHFFFAOYSA-O hydroxy(oxo)azanium Chemical compound O[NH+]=O BLNWTAHYTCHDJH-UHFFFAOYSA-O 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 150000003568 thioethers Chemical class 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims 3
- 238000003786 synthesis reaction Methods 0.000 claims 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 2
- 150000001350 alkyl halides Chemical class 0.000 claims 2
- 150000003556 thioamides Chemical class 0.000 claims 2
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 150000003335 secondary amines Chemical class 0.000 claims 1
- 238000011144 upstream manufacturing Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 125000003441 thioacyl group Chemical group 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- AZTFYJYLDIQSAG-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(propan-2-ylamino)propan-1-one Chemical compound CC(C)NC(C)C(=O)C1=CC=C(Cl)C=C1 AZTFYJYLDIQSAG-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Die Erfindung betrifft ein Verfahren zur Herstellung von 4-(v-Aminoalkyl)thiazolen. Derartige Verbindungen besitzen Bedeutung als Pharmaka, beispielsweise mit magensaftsekretionshemmender Wirkung. Mit der Erfindung soll erreicht werden, 4-(v-Aminoalkyl)thiazole herzustellen, die in v-Position einen monosubstituierten Aminrest tragen, wobei nur ein Verfahrensschritt benoetigt wird und Ausgangsprodukte eingesetzt werden, die noch nicht das Thiazolgeruest enthalten. Dies geschieht erfindungsgemaess in der Weise, dass Thioacyllactamimine mit substituierten Methylhalogeniden und gegebenenfalls einer Base vorteilhafterweise in einem organischen Loesungsmittel zu den 4-(v-Aminoalkyl)thiazolen der allgemeinen Formel I umgesetzt werden. Die Erfindung ist in der chemischen und pharmazeutischen Industrie einsetzbar.The invention relates to a process for the preparation of 4- (v-aminoalkyl) thiazoles. Such compounds have significance as pharmaceuticals, for example with gastric juice secretion-inhibiting effect. The invention is intended to produce 4- (v-aminoalkyl) thiazoles which carry a monosubstituted amine radical in the v position, wherein only one process step is required and starting materials are used which do not yet contain the Thiazolgeruest. This is done according to the invention in such a way that thioacyllactamimines with substituted methyl halides and optionally a base are advantageously reacted in an organic solvent to the 4- (v-aminoalkyl) thiazoles of the general formula I. The invention can be used in the chemical and pharmaceutical industries.
Description
(CH2)n-lHR1 (CH 2 ) n -HR 1
in der R Wasserstoff, einen Alkyl-, Aryl-, Heteroaryl- oder substituierten oder unsubstituierten Aminrest, R1 einen Alkyl-, Aryl- oder Benzylrest, R2 einen elektronenziehenden Rest, wie zum Beispiel einen Aryl-, Vinyl-, Carbonyl-, Sulfonyl-, Heteroaryl-, Cyano- oder Nitrorest und η 3,4 oder 5 darstellen, hergestellt werden durch Umsetzung eines Thioacyllactamimins der allgemeinen Formel Ilin which R is hydrogen, an alkyl, aryl, heteroaryl or substituted or unsubstituted amine radical, R 1 is an alkyl, aryl or benzyl radical, R 2 is an electron-withdrawing radical, for example an aryl, vinyl, carbonyl, Sulfonyl, heteroaryl, cyano or nitro radical and η 3,4 or 5, are prepared by reacting a Thioacyllactamimins of the general formula II
Wi*wi *
R1 SR 1 S
mitderfürR, R1 und η erklärten Bedeutungwith the meaning explained for R, R 1 and η
mit einem substituierten Methylhalogenid der allgemeinen Formel IIIwith a substituted methyl halide of the general formula III
R2-CH2-Hal IIIR 2 -CH 2 -Hal III
mitderfürR2 erklärten Bedeutung und in der Hai für ein Halogen steht und gegebenenfalls mit einer Base, wie zum Beispiel einem Amin, einem Alkalihydroxid oder -alkoholat bzw. einem Metallhydrid, vorteilhafterweise in einem organischen Lösungsmittel.with the meaning explained for R 2 and in the shark a halogen and optionally with a base such as, for example, an amine, an alkali hydroxide or alcoholate or a metal hydride, advantageously in an organic solvent.
Das erfindungsgemäße Verfahren gestattet es, 4-(w-Aminoalkyl)thiazole der allgemeinen Formel I mit monosubstituiertem Aminsubstituenten in ω-Position des 4-ständigen Alkylrestes herzustellen. Die erhaltenen Verbindungen sind neu, sie werden auf dem Wege einer bisher nicht bekannten Ringtransformation in nur einem Reaktionsschritt, der den Aufbau des Thiazolgerüstes und gleichzeitig die Bildung des 4-(a>-Aminoalkyl)-Substituenten einschließt, gewonnen. Überraschenderweise tritt bei der Reaktion des Thioacyllactamimins der allgemeinen Formel Il mit dem Methylhalogenid der allgemeinen Formel III, selbst wenn letzteres im Überschuß angewendet wird, weder eine Alkylierung der 4-(&>-Amino)-Funktion noch eine Alkylierung einer 2-ständigen Aminogruppe ein. Auch werden im Falle von Verbindungen Il (R=NH2) bei der Umsetzung mit substituierten Methylhalogeniden III keine Sulfide unter formaler H2S-Abspaltung erhalten, wie aus dem Stande der Technik zu erwarten war.The process according to the invention makes it possible to prepare 4- (w-aminoalkyl) thiazoles of the general formula I with monosubstituted amine substituents in the ω position of the 4-position alkyl radical. The compounds obtained are novel, they are obtained by way of a hitherto unknown ring transformation in only one reaction step, which includes the construction of the Thiazolgerüstes and simultaneously the formation of the 4- (a> -Aminoalkyl) substituent. Surprisingly, in the reaction of the thioacyl lactamimine of general formula II with the methyl halide of general formula III, even if the latter is used in excess, neither alkylation of the 4 - (-> amino) function nor alkylation of a 2-amino group occurs , Also, in the case of compounds II (R = NH 2 ) in the reaction with substituted methyl halides III no sulfides are obtained with formal H 2 S cleavage, as was expected from the prior art.
Die nach den verschiedenen Varianten hergestellten 4-(co-Aminoalkyl)thiazole der allgemeinen Formel I sind in Tabelle 1 zusammengestellt.The prepared according to the different variants 4- (co-aminoalkyl) thiazoles of the general formula I are summarized in Table 1.
Variante Aoption A
0,1 MolThioacyllactamimin der allgemeinen Formel Il werden mit 25 ml Acetonitril und 0,1 Mol substituiertem Methylhalogenid der allgemeinen Formel Il (HaI=Br) versetzt. Man erhitzt die Mischung 10 Minuten unter Rück'fluß und gibt nach dem Abkühlen 0,2 Mol Triethylamin zu. Anschließend wird die Mischung weitere 5 Minuten unter Rückfluß erhitzt. Das beim Abkühlen aus der Reaktionsmischung ausfallende Endprodukt der allgemeinen Formel I wird abgesaugt und umkristallisiert.0.1 mol of thioacyl lactamimine of the general formula II are admixed with 25 ml of acetonitrile and 0.1 mol of substituted methyl halide of the general formula II (HaI = Br). The mixture is refluxed for 10 minutes and, after cooling, 0.2 mol of triethylamine are added. The mixture is then heated under reflux for a further 5 minutes. The precipitated on cooling from the reaction mixture end product of general formula I is filtered off with suction and recrystallized.
Variante BVariant B
Analog Variante A, jedoch wird ein substituiertes Methylhalogenid der allgemeinen Formel III (HaI=CI) und nur 0,1 Mol Triethylamin verwendet.Analog variant A, but a substituted methyl halide of general formula III (HaI = CI) and only 0.1 mol of triethylamine is used.
Variante CVariant C
Analog Variante A, jedoch ohne Verwendung von Triethylamin. Die Reaktionsmischung wird nach dem Vereinen der Komponenten ohne Unterbrechung 30 Minuten unter Rückfluß erhitzt.Analog variant A, but without the use of triethylamine. The reaction mixture is refluxed for 30 minutes after combining the components without interruption.
Variante DVariant D
Analog Variante A, jedoch wird anstelle des Acetonitrils Methanol als Lösungsmittel verwendet.Analog variant A, but methanol is used as solvent instead of the acetonitrile.
Variante EVariant E
Analog Variante A, jedoch wird anstelle des Triethylamins eine Lösung von 2,3g Natrium in 20ml Methanol verwendet.Analog variant A, but instead of triethylamine, a solution of 2.3 g of sodium in 20 ml of methanol is used.
Variante GVariant G
Eine Mischung von 0,1 MolThioacyllactamimin der allgemeinen Formel II, 25ml Acetonitril, 0,1 Mol substituiertem Methylhalogenid der allgemeinen Formel III (HaI=Br) und 0,2 Mol Triethylamin wird 24 Stunden bei Raumtemperatur stehen gelassen. Anschließend wird wie unter Variante A angegeben aufgearbeitet.A mixture of 0.1 mol of thioacyl lactamimine of the general formula II, 25 ml of acetonitrile, 0.1 mol of substituted methyl halide of the general formula III (HaI = Br) and 0.2 mol of triethylamine is allowed to stand at room temperature for 24 hours. Subsequently, as described under variant A worked up.
Variante HVariant H
Eine Mischung von 0,1 Mol Thioacyllactamimin der allgemeinen Formel II, 25 ml Chloroform und 0,1 Mol substituiertem Methylhalogenid der allgemeinen Formel III (HaI=CI) wird 15 Minuten unter Rückfluß erhitzt. Das gebildete Festprodukt wird abgesaugt und in 20 ml Acetonitril eingetragen. Nach Zugabe von 0,2 Mol Triethylamin wird die Mischung 20 Minuten gekocht.A mixture of 0.1 mole of thioacyl lactamimine of the general formula II, 25 ml of chloroform and 0.1 mole of substituted methyl halide of the general formula III (Hal = Cl) is refluxed for 15 minutes. The solid product formed is filtered off with suction and introduced into 20 ml of acetonitrile. After adding 0.2 mol of triethylamine, the mixture is boiled for 20 minutes.
Das gebildete Endprodukt der allgemeinen Formel I wird abgesaugt und umkristallisiert.The resulting end product of general formula I is filtered off and recrystallized.
Die nach den verschiedenen Varianten hergestellten 4-(co-Aminoalkyl)thiazole der allgemeinen Formel IThe prepared according to the different variants 4- (co-aminoalkyl) thiazoles of the general formula I.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD27434485A DD235642A1 (en) | 1985-03-22 | 1985-03-22 | PROCESS FOR THE PREPARATION OF 4- (OMEGA-AMINOALKYL) THIAZOLENE |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DD27434485A DD235642A1 (en) | 1985-03-22 | 1985-03-22 | PROCESS FOR THE PREPARATION OF 4- (OMEGA-AMINOALKYL) THIAZOLENE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD235642A1 true DD235642A1 (en) | 1986-05-14 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD27434485A DD235642A1 (en) | 1985-03-22 | 1985-03-22 | PROCESS FOR THE PREPARATION OF 4- (OMEGA-AMINOALKYL) THIAZOLENE |
Country Status (1)
| Country | Link |
|---|---|
| DD (1) | DD235642A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012122368A1 (en) * | 2011-03-08 | 2012-09-13 | The Regents Of The University Of California | Deoxycytidine kinase binding compounds |
-
1985
- 1985-03-22 DD DD27434485A patent/DD235642A1/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012122368A1 (en) * | 2011-03-08 | 2012-09-13 | The Regents Of The University Of California | Deoxycytidine kinase binding compounds |
| US9688673B2 (en) | 2011-03-08 | 2017-06-27 | The Regents Of The University Of California | Deoxycytidine kinase binding compounds |
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| ENJ | Ceased due to non-payment of renewal fee |